About PSEN1
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
PSEN1 c.1234G>A, p.(Val412Ile)
Classification
Uncertain significance
Variant description:
No variant summary was recorded for this case.
Five-step scale from benign to pathogenic. This variant is uncertain. Select a step to read what it means.
Uncertain.The recorded classification is uncertain significance.
In plain language
Gene-level background from the recorded interpretation.
Words with a dotted underline have a short definition. Hover or tap them.
LYFE Sciences is an AI system, and it can make mistakes.
Criteria may be applied incorrectly, sources may be misread, and a
confident-looking classification can still be wrong.
Double-check every criterion and its underlying evidence
before relying on any call.
01The reasoning
How it was classified
The recorded framework is Not recorded. The criteria and strengths shown below come from the saved assessment; this page does not recalculate the classification.
Recorded applied criteria
The applied criteria and their strengths are shown as assessed under the stated framework.
Pathogenic evidence criteria: 2
Benign evidence criteria: 0
Pathogenic criteria applied · 2
PM2Supporting
PM2 · supporting
This variant is extremely rare in population databases, well below the 0.1% PM2 threshold. gnomAD v2.1: 3/280,740 alleles (AF=0.00107%); gnomAD v4.1: 23/1,613,504 alleles (AF=0.00143%); grpmax FAF=2.55e-05. Absent from gnomAD-Canada.
PP1Supporting
PP1 · supporting
The variant co-segregates with early-onset frontotemporal dementia in 4 affected individuals over 2 generations in the FUS family (PMID:18314228). However, incomplete penetrance is noted: 2 cognitively healthy elderly carriers were identified (IV-5 at age 49, III-2 at age 71; PMID:21297264), which tempers the segregation signal.
Benign criteria applied · 0
No benign criterion marked as applied in the recorded assessment.
Recorded classification: Uncertain significance
gene-specific framework lacked a usable explicit final combination framework, so generic ACMG/AMP 2015 final-combination rules were applied as fallback; applied criteria: PM2 supporting, PP1 supporting; combination = 2 supporting, which maps to VUS.
02The sources
Evidence at a glance
Evidence summaries and captured source records, where available. Missing entries should not be interpreted as negative findings.
gnomAD v4.1
gnomAD v2.1
Population frequency
23 / 1,613,504 alleles
gnomAD v4.1: 23 / 1,613,504 alleles. Recorded AF 1.42547e-05. Recorded homozygote count 0.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 1.0686e-05; MAF= 0.00107%, 3/280740 alleles, homozygotes = 0) and has highest observed frequency in the African/African American population (AF= 4.09802e-05; MAF= 0.00410%, 1/24402 alleles, homozygotes = 0); grpmax FAF= 2.95e-06.
gnomAD-Canada
Absent from gnomAD-Canada v1.0.
SpliceAI score
0.000 maximum delta
Recorded SpliceAI maximum delta score: 0.000. Refer to the recorded PP3/BP4 rationale for interpretation.
No listed criterion applied
SpliceAI ↗
ClinVar submissions
3 reported laboratory submissions
3 Uncertain significance.
Context only
ClinVar ↗
No screenshot for this evidence
Functional evidence
Not recorded
No standalone functional evidence summary is recorded in evidence_summary.functional.
No listed criterion applied
OncoKB ↗
COSMIC
Cancer Hotspots
Somatic evidence
No matching record reported
This variant has not previously been reported in somatic cancers (COSMIC).
Cancer Hotspots
This variant does not lie in a statistically significant hotspot.
Context only
For specialists
Technical detail
ACMG/AMP criteria under Not recorded, with the data and sources behind each one.
29 criteria with recorded statuses: 2 met · 21 not met · 1 not assessed · 5 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.
Met
Not met
Not assessed
Not applicable
NM_000021.3(PSEN1):c.1234G>A (p.Val412Ile) is extremely rare in population databases, with an allele frequency of 0.00107% in gnomAD v2.1 (3/280,740 alleles) and 0.00143% in gnomAD v4.1 (23/1,613,504 alleles), meeting PM2 at supporting level.
The variant co-segregates with early-onset frontotemporal dementia in 4 affected individuals across 2 generations in the FUS family (Bernardi et al. 2009, PMID:18314228), meeting PP1 at supporting level. However, incomplete penetrance is noted with 2 cognitively healthy carriers identified at ages 49 and 71 in follow-up (Bernardi et al. 2011, PMID:21297264).
No variant-specific functional data are available. The in vitro study of 138 PSEN1 pathogenic mutations by Sun et al. (PMID:27930341) did not include p.Val412Ile, as it is currently classified as a variant of uncertain significance.
In silico predictors are mixed: REVEL score is 0.679, BayesDel is 0.305, and SpliceAI predicts no splicing impact (delta=0.00). The ClinVar submitter LabCorp notes 3 of 5 in silico tools predict a benign effect, precluding application of PP3.
This variant is classified as Uncertain significance by 3 clinical laboratories in ClinVar (ID: 1318725). No submitter classifies it as pathogenic or likely pathogenic.
Overall, the evidence for pathogenicity is limited to one supporting criterion (PM2) and one supporting criterion (PP1). With only 2 supporting criteria met and no moderate or strong pathogenic criteria, the variant does not reach the threshold for Likely Pathogenic (which requires 2 supporting + 1 moderate, or variants thereof). The classification remains Uncertain significance.
No criteria match.
Met · 2
PM2 SupportingThis variant is extremely rare in population databases, well below the 0.1% PM2 threshold. gnomAD v2.1: 3/280,740 alleles (AF=0.00107%); gnomAD v4.1: 23/1,613,504 alleles (AF=0.00143%); grpmax FAF=2.55e-05. Absent from gnomAD-Canada. Details ▾Hide ▴
Evidence considered
- gnomAD v2.1 AF=0.00107% (3/280
- 740)
- gnomAD v4.1 AF=0.00143% (23/1
- 613
- 504)
- gnomAD-Canada absent
- all well below 0.1% PM2 threshold
- no homozygotes.
Sources
PP1 SupportingThe variant co-segregates with early-onset frontotemporal dementia in 4 affected individuals over 2 generations in the FUS family (PMID:18314228). However, incomplete penetrance is noted: 2 cognitively healthy elderly carriers were identified (IV-5 at age 49, III-2 at age 71; PMID:21297264), which tempers the segregation signal. Details ▾Hide ▴
Evidence considered
- Co-segregation in 4 affected across 2 generations of FUS family (Bernardi et al. 2009). Two healthy carriers at ages 49 and 71 reported in follow-up (Bernardi et al. 2011)
- indicating incomplete penetrance.
Still missing
- Co-occurring PRNP insertion mutation in some family members complicates genotype-phenotype correlation.
Sources
Not met · 21 · evaluated, threshold not reached
PVS1 NM_000021.3:c.1234G>A is a missense variant (p.Val412Ile), not a null variant (nonsense, frameshift, or canonical splice). Generic PVS1 framework requires null-variant types; this substitution does not qualify. Details ▾Hide ▴
Evidence considered
- Missense variant does not meet PVS1 null-variant criteria per ClinGen SVI PVS1 recommendations (PMC6185798).
Sources
pvs1_variant_assessmentpvs1_gene_context
PS1 No pathogenic variant at the same nucleotide position (c.1234) has been identified. PS1 requires a different nucleotide change at the same position that is known to be pathogenic. Details ▾Hide ▴
Evidence considered
- No alternative pathogenic substitution at c.1234 identified in ClinVar or literature.
Sources
clinvar ↗pm5_candidates
PS2 No confirmed de novo occurrence with maternity and paternity confirmation has been reported for this variant. Details ▾Hide ▴
Evidence considered
- No de novo observation identified in any reviewed publication or database.
Still missing
- No de novo testing data available.
PS3 No variant-specific functional data are available. The in vitro γ-secretase assay by Sun et al. (PMID:27930341) analyzed 138 pathogenic PSEN1 mutations; p.Val412Ile, currently classified as VUS, was not among the variants studied. Details ▾Hide ▴
Evidence considered
- PMID:27930341 studied 138 pathogenic PSEN1 mutations but did not include p.Val412Ile.
Still missing
- No variant-specific functional assay data exist for this variant.
Sources
PS4 The variant has been observed in a single family (FUS family) with 4 affected individuals across 2 generations. No case-control study or statistically significant enrichment in affected vs. control populations is available. Details ▾Hide ▴
Evidence considered
- Observed in 4 affected members of one autosomal dominant early-onset FTD family (FUS pedigree). No case-control prevalence data available.
Still missing
- No case-control prevalence data
- limited to one reported family.
Sources
PM1 Residue 412 does not lie in a statistically significant mutational hotspot (hotspots residue_significant: false). No domain-level evidence establishes codon 412 as a critical functional domain without benign variation. Details ▾Hide ▴
Evidence considered
- Hotspot analysis: residue not significant
- exact variant not listed as hotspot. No functional domain criteria met.
PM5 No pathogenic missense variant at the same amino acid residue (Val412) has been identified. Automated PM5 candidate search found zero same-residue pathogenic comparators. Details ▾Hide ▴
Evidence considered
- PM5 candidate harvest returned zero same-residue pathogenic comparator variants. No ClinVar pathogenic variant at codon 412.
Sources
pm5_candidates
PM6 No de novo observation (with or without confirmed parentage) has been reported for this variant in any reviewed source. Details ▾Hide ▴
Evidence considered
- No de novo observation identified in publications or databases.
Still missing
- No de novo testing data available.
PP3 In silico predictors yield mixed results, not meeting the threshold for multiple lines of computational evidence supporting a deleterious effect. REVEL score is 0.679 (borderline), BayesDel is 0.305 (marginally above the 0.27 damaging threshold), but ClinVar submitter LabCorp notes 3 of 5 in silico tools predict a benign effect. SpliceAI predicts no splicing impact (max delta=0.00). Details ▾Hide ▴
Evidence considered
- REVEL=0.679 (borderline)
- BayesDel=0.305
- SpliceAI=0.00
- ClinVar submission notes 3/5 tools predict benign. No consensus across predictors.
Sources
PP4 The proband's phenotype (early-onset frontotemporal dementia) is not highly specific for PSEN1-related disease. FTD has significant genetic heterogeneity (MAPT, PGRN, C9orf72, etc.) and overlapping clinical features with other neurodegenerative conditions. Details ▾Hide ▴
Evidence considered
- FTD phenotype is genetically heterogeneous
- not pathognomonic for PSEN1-related disease.
Sources
PP5 No reputable source (e.g., clinical laboratory with appropriate quality measures, expert panel, or clinical database) has classified this variant as pathogenic. Current ClinVar classification is Uncertain significance. Details ▾Hide ▴
Evidence considered
- ClinVar classification: Uncertain significance (3 clinical laboratories). No submission classifies as pathogenic.
Sources
BA1 Allele frequency is far below the 1% BA1 threshold. gnomAD v2.1 AF=0.00107%, gnomAD v4.1 AF=0.00143%. Details ▾Hide ▴
Evidence considered
- Maximum population AF=0.00667% (gnomAD v4.1 African/African American)
- well below 1% BA1 threshold.
Sources
BS1 Allele frequency is far below the 0.3% BS1 threshold. gnomAD v2.1 AF=0.00107%, gnomAD v4.1 AF=0.00143%. Details ▾Hide ▴
Evidence considered
- Maximum population AF=0.00667% (gnomAD v4.1 African/African American)
- well below 0.3% BS1 threshold.
Sources
BS2 Two cognitively healthy elderly carriers of PSEN1 p.Val412Ile were observed in the FUS family (ages 49 and 71; PMID:21297264). However, PSEN1-associated disease exhibits age-dependent penetrance with reported onset as late as 78 years. Observation of healthy carriers at these ages, while notable, is insufficient to rule out pathogenic potential given the known variable penetrance and age-dependent expressivity of PSEN1 variants. Details ▾Hide ▴
Evidence considered
- Two healthy carriers at ages 49 (IV-5) and 71 (III-2) identified in FUS family follow-up. PSEN1 has age-dependent penetrance
- late-onset carriers are known.
Still missing
- Continued surveillance of healthy carriers would clarify age-related penetrance.
Sources
BS3 No well-established functional studies demonstrate a benign effect for this specific variant. Details ▾Hide ▴
Evidence considered
- No variant-specific functional studies showing benign effect available.
Still missing
- No functional data (benign or damaging) exist for this variant.
BS4 The variant segregates with disease in the FUS family (4 affected carriers). Lack of segregation is not observed; two healthy carriers reflect incomplete penetrance, not non-segregation. Details ▾Hide ▴
Evidence considered
- Variant segregates with affected status in FUS family. Healthy carriers represent reduced/incomplete penetrance rather than non-segregation.
Sources
BP2 Not observed in trans with a known pathogenic PSEN1 variant. No data available to assess this criterion. Details ▾Hide ▴
Evidence considered
- No observation in trans with a pathogenic PSEN1 variant in any database or publication.
BP4 Computational evidence is mixed and does not provide multiple lines of support for a benign effect. REVEL 0.679 and BayesDel 0.305 both lean toward damaging, not benign. SpliceAI predicts no splicing impact but this alone is insufficient for BP4. Details ▾Hide ▴
Evidence considered
- REVEL=0.679 (slightly damaging)
- BayesDel=0.305 (marginally damaging). Mixed signals do not meet BP4 threshold for benign computational evidence.
Sources
BP5 No case has been identified where this variant is found in an individual with an alternate definitive molecular cause explaining the phenotype. The PRNP co-mutation in the FUS family does not constitute an alternate cause, as PSEN1-only carriers were also affected. Details ▾Hide ▴
Evidence considered
- PRNP insertion co-occurred in some FUS family members but PSEN1-only carriers (IV-1) were also affected
- ruling out PRNP as the sole disease cause.
Sources
BP6 No reputable source classifies this variant as benign. ClinVar consensus is Uncertain significance (3 laboratories, criteria provided, single submitter). Details ▾Hide ▴
Evidence considered
- ClinVar classification: Uncertain significance. No benign classification from any submitter.
Sources
PS5 No evidence from genome-wide association or linkage studies establishes this specific variant as disease-causing. Details ▾Hide ▴
Evidence considered
- No GWAS or definitive linkage data for this specific variant.
Still missing
- No genome-wide or linkage data for this specific variant.
Not assessed · 1 · no assessment recorded
PP2 Insufficient gene-level constraint metrics for PSEN1 available in this case. PP2 requires a gene with low rate of benign missense variation and high rate of pathogenic missense variants, but gnomAD missense constraint scores (Z-score) were not provided. Details ▾Hide ▴
Evidence considered
- No gnomAD missense constraint Z-score or comparable metric available to assess PP2.
Still missing
- gnomAD missense constraint metrics not available
- requires gene-level Z-score data.
Not applicable · 5· recorded as not applicable Show reasons ▾Hide reasons ▴
PM3 N/APSEN1-associated disease is autosomal dominant; PM3 (observation in trans with a pathogenic variant) is not applicable to dominant disorders with established dominant mechanism. Details ▾Hide ▴
No further detail was recorded.
PM4 N/AVariant is a single-nucleotide missense substitution, not a protein-length-altering change (in-frame deletion/insertion, stop-loss, or initiation codon). Details ▾Hide ▴
No further detail was recorded.
BP1 N/APSEN1-associated disease is primarily driven by missense variants, not truncating variants. BP1 applies only to genes where truncating variants are the predominant disease mechanism. Details ▾Hide ▴
No further detail was recorded.
BP3 N/AVariant is a single-nucleotide substitution, not an in-frame indel; BP3 applies exclusively to in-frame deletions/insertions in repetitive regions. Details ▾Hide ▴
No further detail was recorded.
BP7 N/ANM_000021.3:c.1234G>A is a missense variant (p.Val412Ile), not a synonymous or intronic variant. BP7 applies only to synonymous variants without predicted splicing impact. Details ▾Hide ▴
No further detail was recorded.
Identifiers
- Gene
- PSEN1
- Transcript
- NM_000021.3
- Coding (HGVS c.)
- NM_000021.3:c.1234G>A
- Protein (HGVS p.)
- NP_000012.1:p.(Val412Ile)
- GRCh38
- chr14:73217230 G>A
- GRCh37
- chr14:73683938 G>A
- ClinVar
- 1318725
Gene diagram
Every interpreted variant in PSEN1, mapped onto the exon structure of NM_000021.3. Select a row to find it on the plot.
PSEN1NM_000021.3
Fetching transcript structure from UCSC…
Exons
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Transcript span
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Strand
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Variants mapped
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Source
UCSC ncbiRefSeqCurated
All variants in PSEN1
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Select a row to find it on the plot; use the link to open its page.
| Protein | Location | Classification | Link |
|---|
gnomAD v4.1
23 / 1,613,504 alleles
AF 1.43e-05 · 0 homozygotes · FAF 2.55e-05
gnomAD v2.1
3 / 280,740 alleles
AF 1.07e-05 · 0 homozygotes · FAF 2.95e-06
gnomAD-Canada v1.0
Allele count data not recorded
By genetic ancestry
gnomAD v4.1
AF 1.4e-05 · 23 / 1,613,504 alleles · 0 hom · FAF 2.6e-05
| African/African American5 / 74,908 | 6.7e-05 |
| South Asian2 / 91,082 | 2.2e-05 |
| Remaining individuals1 / 62,422 | 1.6e-05 |
| European (non-Finnish)15 / 1,179,924 | 1.3e-05 |
0 alternate alleles recorded in 6 other groups: Admixed American, European (Finnish), Amish, East Asian, Middle Eastern, Ashkenazi Jewish.
gnomAD v2.1
AF 1.1e-05 · 3 / 280,740 alleles · 0 hom · FAF 3e-06
| African/African American1 / 24,402 | 4.1e-05 |
| European (non-Finnish)2 / 128,152 | 1.6e-05 |
0 alternate alleles recorded in 6 other groups: Admixed American, Ashkenazi Jewish, East Asian, European (Finnish), Remaining individuals, South Asian.
Statements
gnomAD v4.1
This variant is present in gnomAD v4.1 (AF= 1.42547e-05; MAF= 0.00143%, 23/1613504 alleles, homozygotes = 0) and has highest observed frequency in the African/African American population (AF= 6.67485e-05; MAF= 0.00667%, 5/74908 alleles, homozygotes = 0); grpmax FAF= 2.55e-05.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 1.0686e-05; MAF= 0.00107%, 3/280740 alleles, homozygotes = 0) and has highest observed frequency in the African/African American population (AF= 4.09802e-05; MAF= 0.00410%, 1/24402 alleles, homozygotes = 0); grpmax FAF= 2.95e-06.
gnomAD-Canada
Absent from gnomAD-Canada v1.0.
SpliceAI and Pangolin
Other predictors
- REVEL
- 0.679
- BayesDel
- 0.305
How the predictions were used
PP3 In silico predictors yield mixed results, not meeting the threshold for multiple lines of computational evidence supporting a deleterious effect. REVEL score is 0.679 (borderline), BayesDel is 0.305 (marginally above the 0.27 damaging threshold), but ClinVar submitter LabCorp notes 3 of 5 in silico tools predict a benign effect. SpliceAI predicts no splicing impact (max delta=0.00). Details ▾Hide ▴
Evidence considered
- REVEL=0.679 (borderline)
- BayesDel=0.305
- SpliceAI=0.00
- ClinVar submission notes 3/5 tools predict benign. No consensus across predictors.
Sources
BP4 Computational evidence is mixed and does not provide multiple lines of support for a benign effect. REVEL 0.679 and BayesDel 0.305 both lean toward damaging, not benign. SpliceAI predicts no splicing impact but this alone is insufficient for BP4. Details ▾Hide ▴
Evidence considered
- REVEL=0.679 (slightly damaging)
- BayesDel=0.305 (marginally damaging). Mixed signals do not meet BP4 threshold for benign computational evidence.
Sources
BP7 N/ANM_000021.3:c.1234G>A is a missense variant (p.Val412Ile), not a synonymous or intronic variant. BP7 applies only to synonymous variants without predicted splicing impact. Details ▾Hide ▴
No further detail was recorded.
Statement
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00). REVEL score = 0.679. BayesDel score = 0.305405.
5 paper records listed. 2 cited in the classification.
Cited in the classification
-
PMID 18314228 ↗Novel PSEN1 and PGRN mutations in early-onset familial frontotemporal dementia.Bernardi L et al. · 2009 NovIdentified PSEN1 Val412Ile as a novel heterozygous mutation in an autosomal dominant early-onset frontotemporal dementia family (FUS pedigree). The proband, a 38-year-old female, developed progressive mood and personality changes at age 30 with subsequent cognitive decline, mutism, myoclonus, and seizures. Four affected individuals across two generations carried the mutation. Mutation was absent from 100 cognitively healthy controls and 100 previously screened familial Alzheimer disease patients.→ PP1 Names this variant
Source detail
Val412Ile is a heterozygous transition in exon 11 (g.69148G>A according to GenBank accession number AF109907.1; c.1234 according to GenBank accession number NM 000021.2) of the PSEN1 gene in the first position of codon 412, which predicts an aminoacidic substitution from valine to isoleucine and it was detected in a 38-year-old female (FUS family).
Location Abstract; Results, sections 3.1-3.2; Figure 2; Figure 3A pedigree; Discussion
Context DHPLC screening and Sanger sequencing of PSEN1 exons 3-12 in 17 f-EOFTD patients; RFLP and DHPLC for control validation
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PMID 21297264 ↗PSEN1 and PRNP gene mutations: co-occurrence makes onset very early in a family with FTD phenotype.Bernardi L et al. · 2011Follow-up study of the FUS family originally reported in Bernardi et al. 2009. Identified a novel seven extra-repeat PRNP insertional mutation co-occurring with PSEN1 Val412Ile. PSEN1 Val412Ile alone was found in 2 affected and 2 cognitively healthy carriers (ages 49 and 71), demonstrating incomplete penetrance. Double carriers (PSEN1 + PRNP) had very early onset within the third decade. Both mutations showed variable penetrance when present separately.→ PP1 Names this variant
Source detail
The PSEN1 Val412Ile mutation, which was previously detected in the three patients [14], was also identified in two additional family members (IV-5, III-2, in this paper).
Location Abstract; Results; Table 1; Figure 1 pedigree; Discussion
Context Bidirectional sequencing of PRNP and PSEN1 genes; APOE genotyping, MAPT haplotype analysis, PRNP M129V polymorphism assessment
Other recorded publications
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PMID 25741868 ↗Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.Richards S et al. · 2015ACMG/AMP joint consensus guidelines for the interpretation of sequence variants. Provides the framework for variant classification but contains no variant-specific data for PSEN1 p.Val412Ile or any other specific PSEN1 variant.Does not name this variant
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PMID 27930341 ↗Analysis of 138 pathogenic mutations in presenilin-1 on the in vitro production of Aβ42 and Aβ40 peptides by γ-secretase.Sun L et al. · 2017Comprehensive in vitro analysis of 138 pathogenic PSEN1 mutations on Aβ42 and Aβ40 production by γ-secretase using purified recombinant protein in HEK293 cells. Established a linear correlation between Aβ42/Aβ40 ratio and clinical age at onset. p.Val412Ile, currently classified as a VUS, was not among the 138 pathogenic mutations studied.Does not name this variant
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PMID 29091718 ↗Analysis of neurodegenerative Mendelian genes in clinically diagnosed Alzheimer Disease.Fernández MV et al. · 2017Investigated Mendelian neurodegenerative disease genes (APP, PSEN1, PSEN2, MAPT, GRN, TARDBP, FUS, etc.) in clinically diagnosed Alzheimer disease cases. Identified 4 known pathogenic mutations and several VUS, but p.Val412Ile was not among the variants reported.Does not name this variant
Screenshots represent source records captured during evidence collection. Select one to view the recorded source content.
gnomAD v4.1
23 / 1,613,504 recorded alleles
Open source ↗
gnomAD v2.1
Captured gnomAD v2.1 source record
Open source ↗
SpliceAI Lookup
Recorded maximum delta 0.000
Open source ↗
ClinVar
3 Uncertain significance
Open source ↗
COSMIC
Captured COSMIC source record
Open source ↗
Cancer hotspots
Captured Cancer Hotspots source record
Open source ↗
All source links
- ClinVar ↗www.ncbi.nlm.nih.gov/clinvar/variation/1318725/
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/14-73683938-G-A?dataset=gnomad_r2_1
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr14-73217230-G-A?dataset=gn…
- gnomAD-Canada ↗http://192.168.4.76:8001/variant/14-73217230-G-A
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_000021.3%3Ac.1234…
- OncoKB ↗www.oncokb.org/gene/PSEN1/V412I
- COSMIC ↗cancer.sanger.ac.uk/cosmic/search?q=PSEN1+c.1234G%3EA
- Cancer hotspots ↗www.cancerhotspots.org/
Statements for reports
The evidence statements recorded by the interpretation pipeline. They have not been reinterpreted by the page.
gnomAD v4.1
This variant is present in gnomAD v4.1 (AF= 1.42547e-05; MAF= 0.00143%, 23/1613504 alleles, homozygotes = 0) and has highest observed frequency in the African/African American population (AF= 6.67485e-05; MAF= 0.00667%, 5/74908 alleles, homozygotes = 0); grpmax FAF= 2.55e-05.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 1.0686e-05; MAF= 0.00107%, 3/280740 alleles, homozygotes = 0) and has highest observed frequency in the African/African American population (AF= 4.09802e-05; MAF= 0.00410%, 1/24402 alleles, homozygotes = 0); grpmax FAF= 2.95e-06.
gnomAD-Canada
Absent from gnomAD-Canada v1.0.
ClinVar
This variant has been reported in ClinVar as Uncertain significance (3 clinical laboratories). (ClinVarID = 1318725)
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00). REVEL score = 0.679. BayesDel score = 0.305405.
Somatic
This variant does not lie in a statistically significant hotspot. This variant has not previously been reported in somatic cancers (COSMIC).
Cancer Hotspots
This variant does not lie in a statistically significant hotspot.