About PIK3CA
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
PIK3CA c.1173A>G, p.(Ile391Met)
Classification
Benign
Variant description:
No variant summary was recorded for this case.
Five-step scale from benign to pathogenic. This variant is benign. Select a step to read what it means.
Benign.A benign classification under the recorded framework.
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 ClinGen PIK3CA VCEP v1.1.0. 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: 1
Benign evidence criteria: 4
Pathogenic criteria applied · 1
PM1Supporting
PM1 · supporting
The p.Ile391Met change lies within the PIK3CA amino-acid interval 322-483, which is listed by this VCEP as an approved Table 4 critical functional domain, supporting PM1 at Supporting strength. Cancer Hotspots did not identify a statistically significant hotspot at residue 391, but hotspot recurrence is not required by this VCEP when the variant falls in an approved domain.
Benign criteria applied · 4
BA1Stand alone
BA1 · stand alone
This variant exceeds the VCEP BA1 threshold of greater than 0.0926% by a wide margin, with overall allele frequency 6.57058% in gnomAD v2.1 and 6.60819% in gnomAD v4.1.
BS1Strong
BS1 · strong
This variant exceeds the VCEP BS1 threshold of greater than 0.0185%, with overall allele frequency 6.57058% in gnomAD v2.1 and 6.60819% in gnomAD v4.1, which is far above the maximum expected frequency for a disease-causing PIK3CA brain malformation variant.
BS2Strong
BS2 · strong
This variant is present in many apparently healthy population participants, including 1,032 homozygotes in gnomAD v2.1 and 4,921 homozygotes in gnomAD v4.1, which is well above the VCEP BS2 threshold of at least 3 homozygotes.
BP6Supporting
BP6 · supporting
Expert panel ClinGen Brain Malformations Variant Curation Expert Panel classified as Benign.
Recorded classification: Benign
Brain Malformations Specification Tavtigian point framework v1.1.0 point-based framework: BS2 strong (-4) + PM1 supporting (+1) + BA1 stand-alone benign (-8) + BS1 strong (-4) = -15 points, which maps to Benign.
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
106,360 / 1,609,518 alleles
gnomAD v4.1: 106,360 / 1,609,518 alleles. Recorded AF 0.0660819. Recorded homozygote count 4921.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 0.0657058; MAF= 6.57058%, 18372/279610 alleles, homozygotes = 1032) and has highest observed frequency in the African/African American population (AF= 0.211283; MAF= 21.12834%, 5097/24124 alleles, homozygotes = 531); grpmax FAF= 0.204728.
No screenshot for this evidence
Computational predictions
Not recorded
No SpliceAI or REVEL score is recorded in the fields used for this tile.
No listed criterion applied
ClinVar submissions
Not recorded
A ClinVar laboratory submission summary was not recorded.
Functional evidence
Statement recorded
OncoKB identified variant-specific curated literature and context relevant to functional review; biological-effect context: Inconclusive; curated oncogenicity label: Inconclusive.
No listed criterion applied
OncoKB ↗
COSMIC
Cancer Hotspots
Somatic evidence
Not assessed
No COSMIC evidence statement is recorded in this case.
Cancer Hotspots
This variant does not lie in a statistically significant hotspot.
Context only
For specialists
Technical detail
ACMG/AMP criteria under ClinGen PIK3CA VCEP v1.1.0, with the data and sources behind each one.
28 criteria with recorded statuses: 5 met · 2 not met · 8 not assessed · 13 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.
Met
Not met
Not assessed
Not applicable
The PIK3CA c.1173A>G (p.Ile391Met) variant has been reported in ClinVar as Benign, including a Benign expert-panel classification from the ClinGen Brain Malformations Variant Curation Expert Panel.
This variant is common in population databases, with allele frequency 6.57058% in gnomAD v2.1 and 6.60819% in gnomAD v4.1, greatly exceeding the VCEP BA1 threshold of 0.0926% and BS1 threshold of 0.0185%, and it is also observed in numerous homozygous individuals.
Curated literature resources identified functional publications relevant to this variant, but the retrieved evidence did not provide validated variant-specific assay results sufficient to apply either PS3 or BS3.
SpliceAI predicts no significant splice impact for this variant with a maximum delta score of 0.00, while REVEL is 0.236 and BayesDel is -0.391355; however, PP3 is not applicable and BP4 is restricted to non-missense variants in this VCEP framework.
No criteria match.
Met · 5
PM1 SupportingThe p.Ile391Met change lies within the PIK3CA amino-acid interval 322-483, which is listed by this VCEP as an approved Table 4 critical functional domain, supporting PM1 at Supporting strength. Cancer Hotspots did not identify a statistically significant hotspot at residue 391, but hotspot recurrence is not required by this VCEP when the variant falls in an approved domain. Details ▾Hide ▴
Rule
PM1_Supporting may be awarded for residues affecting VCEP-approved critical functional domains in Table 4.
Evidence considered
- Variant protein consequence p.Ile391Met
- VCEP Table 4 domain interval 322-483 for PIK3CA
- Cancer Hotspots showed no significant hotspot row
Still missing
- Residue-level hotspot evidence was not confirmed
- but the VCEP domain-based PM1 rule does not require hotspot recurrence.
Sources
BA1 Stand aloneThis variant exceeds the VCEP BA1 threshold of greater than 0.0926% by a wide margin, with overall allele frequency 6.57058% in gnomAD v2.1 and 6.60819% in gnomAD v4.1. Details ▾Hide ▴
Rule
BA1 is met when allele frequency is greater than 0.0926% under this VCEP.
Evidence considered
- VCEP BA1 threshold >0.0926%
- gnomAD v2.1 AF 0.0657058
- gnomAD v4.1 AF 0.0660819
Sources
BS1 StrongThis variant exceeds the VCEP BS1 threshold of greater than 0.0185%, with overall allele frequency 6.57058% in gnomAD v2.1 and 6.60819% in gnomAD v4.1, which is far above the maximum expected frequency for a disease-causing PIK3CA brain malformation variant. Details ▾Hide ▴
Rule
BS1 is met when allele frequency is greater than 0.0185% under this VCEP.
Evidence considered
- VCEP BS1 threshold >0.0185%
- gnomAD v2.1 AF 0.0657058
- gnomAD v4.1 AF 0.0660819
Sources
BS2 StrongThis variant is present in many apparently healthy population participants, including 1,032 homozygotes in gnomAD v2.1 and 4,921 homozygotes in gnomAD v4.1, which is well above the VCEP BS2 threshold of at least 3 homozygotes. Details ▾Hide ▴
Rule
Award BS2 if >=3 homozygotes are present in gnomAD or ExAC, or >=3 heterozygous well-phenotyped family members are observed.
Evidence considered
- gnomAD v2.1 homozygotes = 1032
- gnomAD v4.1 homozygotes = 4921
- VCEP BS2 threshold >=3 homozygotes
Sources
BP6 SupportingExpert panel ClinGen Brain Malformations Variant Curation Expert Panel classified as Benign. Details ▾Hide ▴
Not met · 2 · evaluated, threshold not reached
PS4 PS4 is not met because this VCEP requires PM2 before phenotype-point assignment, and this variant is common in population databases rather than rare or absent from controls. Details ▾Hide ▴
Rule
PS4 phenotype points can only be used if the variant meets PM2.
Evidence considered
- PS4 requires PM2 first under this VCEP
- gnomAD v2.1 AF 0.0657058
- gnomAD v4.1 AF 0.0660819
Sources
PM2 PM2 is not met because this variant is not rare in population databases. Its overall allele frequency is 6.57058% in gnomAD v2.1 and 6.60819% in gnomAD v4.1, far above a one-person maximum or rare-control expectation. Details ▾Hide ▴
Rule
PM2_Supporting requires absence or rarity in controls under this VCEP.
Evidence considered
- gnomAD v2.1 AF 0.0657058
- gnomAD v4.1 AF 0.0660819
- VCEP PM2 requires absent/rare from controls
Sources
Not assessed · 8 · no assessment recorded
PS1 No independently verified evidence was identified showing that this variant causes the same amino acid change as a previously established pathogenic PIK3CA variant by a different nucleotide substitution. Details ▾Hide ▴
Rule
PS1 applies only if the same amino acid change has already been established as pathogenic regardless of nucleotide change.
Evidence considered
- Brain Malformations VCEP PS1 rule reviewed
- No exact same-amino-acid pathogenic match documented in the retrieved materials
Still missing
- A codon-level review for other pathogenic substitutions causing p.Ile391Met was not available in the retrieved evidence.
Sources
cspec ↗vcep_clingen_brainmalform_acmg_specifications_v1_1
PS2 No confirmed de novo evidence with parental testing and tissue-distribution data was identified for this variant, so the VCEP PS2 requirements were not met from the retrieved evidence. Details ▾Hide ▴
Rule
PS2 requires confirmed parental absence, with stronger evidence when tissue distribution supports a post-zygotic event.
Evidence considered
- Brain Malformations VCEP PS2 criteria reviewed
- Exploratory follow-up noted missing parental and tissue-specific confirmation
Still missing
- No case-level documentation of confirmed maternity and paternity was identified.
- No verified comparison of variant allele fraction across affected and unaffected tissues was identified.
Sources
cspec ↗vcep_clingen_brainmalform_acmg_specifications_v1_1
PS3 Curated literature resources identified functional publications relevant to this variant, but the retrieved evidence did not provide validated variant-specific assay results sufficient to support a damaging effect under the VCEP PS3 requirements. Details ▾Hide ▴
Rule
PS3 requires well-established functional studies supporting a damaging effect on protein function or splicing.
Evidence considered
- OncoKB functional literature pointers
- No validated damaging functional result in retrieved evidence
Still missing
- No directly reviewed variant-specific functional study meeting VCEP/SVI quality requirements was identified.
Sources
PM5 No independently verified evidence was identified showing that a different missense change at residue Ile391 has been established as pathogenic. Details ▾Hide ▴
Rule
PM5 applies when a novel missense change occurs at a residue where a different pathogenic missense change has already been established.
Evidence considered
- Brain Malformations VCEP PM5 rule reviewed
Still missing
- A residue-specific review for other pathogenic missense substitutions at codon 391 was not available in the retrieved evidence.
Sources
cspec ↗vcep_clingen_brainmalform_acmg_specifications_v1_1
PP2 PP2 could be considered for PIK3CA missense variants in this VCEP, but no gene-level missense constraint z-score was provided in the retrieved evidence to compare with the required threshold of greater than 3.09. Details ▾Hide ▴
Rule
Award PP2 if the missense constraint z-score is >3.09 for applicable genes including PIK3CA.
Evidence considered
- VCEP PP2 threshold z-score >3.09 reviewed
- No z-score available in retrieved materials
Still missing
- No missense constraint z-score for PIK3CA was identified in the retrieved evidence.
Sources
cspec ↗vcep_clingen_brainmalform_acmg_specifications_v1_1
BS3 Curated literature resources identified functional publications relevant to this variant, but the retrieved evidence did not provide validated variant-specific studies demonstrating a normal or no-damaging effect sufficient for BS3. Details ▾Hide ▴
Rule
BS3 requires well-established functional studies showing no damaging effect on protein function or splicing.
Evidence considered
- OncoKB functional literature pointers
- No validated benign functional result in retrieved evidence
Still missing
- No directly reviewed variant-specific functional assay showing no damaging effect was identified.
Sources
BP2 No phase data were identified showing that this variant was observed in cis or trans with a known pathogenic PIK3CA variant. Details ▾Hide ▴
Rule
BP2 may be used when a variant is observed in cis or trans with a known pathogenic variant in the same gene.
Evidence considered
- Brain Malformations VCEP BP2 rule reviewed
Still missing
- No case-level phase information with another pathogenic PIK3CA variant was identified.
Sources
cspec ↗vcep_clingen_brainmalform_acmg_specifications_v1_1
BP5 No independently verified evidence was identified showing that this variant was found in a case with an alternate molecular basis that explains the reported phenotype. Details ▾Hide ▴
Rule
BP5 may be used when an alternate molecular basis for disease is identified.
Evidence considered
- Brain Malformations VCEP BP5 rule reviewed
Still missing
- No case-level alternate molecular diagnosis data were identified.
Sources
cspec ↗vcep_clingen_brainmalform_acmg_specifications_v1_1
Not applicable · 13· recorded as not applicable Show reasons ▾Hide reasons ▴
PVS1 N/APVS1 is not applicable in this VCEP because PIK3CA-related brain malformations are interpreted under a gain-of-function framework, and this missense variant is also outside the generic null-variant PVS1 categories. Details ▾Hide ▴
Rule
PVS1 is not applicable for this VCEP.
Evidence considered
- VCEP PVS1 not applicable for GOF mechanism
- Generic PVS1 scaffold classified this variant as non-null
Sources
PM3 N/APM3 is not applicable because this disorder framework does not use recessive trans observations for PIK3CA-associated disease. Details ▾Hide ▴
Rule
Not applicable for this VCEP.
Evidence considered
- Brain Malformations VCEP PM3 applicability statement
Sources
cspec ↗vcep_clingen_brainmalform_acmg_specifications_v1_1
PM4 N/APM4 is not applicable in this VCEP. Details ▾Hide ▴
Rule
Not applicable for this VCEP.
Evidence considered
- Brain Malformations VCEP PM4 applicability statement
Sources
cspec ↗vcep_clingen_brainmalform_acmg_specifications_v1_1
PM6 N/APM6 is not applicable in this VCEP because de novo evidence is handled through the PS2 framework instead. Details ▾Hide ▴
Rule
Not applicable for this VCEP.
Evidence considered
- Brain Malformations VCEP PM6 applicability statement
Sources
cspec ↗vcep_clingen_brainmalform_acmg_specifications_v1_1
PP1 N/APP1 is not applicable in this VCEP because disease-causing variants are typically germline mosaic, de novo, or post-zygotic rather than segregation-based familial findings. Details ▾Hide ▴
Rule
Not applicable for this VCEP.
Evidence considered
- Brain Malformations VCEP PP1 applicability statement
Sources
cspec ↗vcep_clingen_brainmalform_acmg_specifications_v1_1
PP3 N/APP3 is not applicable in this VCEP for PIK3CA gain-of-function disease mechanisms. Computational results were reviewed, including REVEL 0.236, BayesDel -0.391355, and SpliceAI max delta 0.00, but the specification does not use PP3 for these missense gain-of-function variants. Details ▾Hide ▴
Rule
PP3 is not applicable for this VCEP because traditional prediction algorithms are not used for these GOF variants.
Evidence considered
- REVEL score 0.236
- BayesDel score -0.391355
- SpliceAI max delta 0.00
- VCEP PP3 not applicable for GOF variants
Sources
PP4 N/APP4 is not applicable in this VCEP because phenotype specificity is incorporated into the point-based PS4 framework rather than used as an independent criterion. Details ▾Hide ▴
Rule
Not applicable for this VCEP.
Evidence considered
- Brain Malformations VCEP PP4 applicability statement
Sources
cspec ↗vcep_clingen_brainmalform_acmg_specifications_v1_1
PP5 N/APP5 is not applicable because this VCEP does not permit use of reputable-source assertions without independent evidence review. Details ▾Hide ▴
Rule
PP5 is not for use in this VCEP.
Evidence considered
- Brain Malformations VCEP PP5 applicability statement
Sources
cspec ↗vcep_clingen_brainmalform_acmg_specifications_v1_1
BS4 N/ABS4 is not applicable in this VCEP because PIK3CA-related brain malformation cases are typically de novo, germline mosaic, or post-zygotic rather than segregation-based familial presentations. Details ▾Hide ▴
Rule
Not applicable for this VCEP.
Evidence considered
- Brain Malformations VCEP BS4 applicability statement
Sources
cspec ↗vcep_clingen_brainmalform_acmg_specifications_v1_1
BP1 N/ABP1 is not applicable because the disease mechanism for this VCEP is gain of function rather than primarily truncating loss-of-function variation. Details ▾Hide ▴
Rule
Not applicable for this VCEP.
Evidence considered
- Brain Malformations VCEP BP1 applicability statement
Sources
cspec ↗vcep_clingen_brainmalform_acmg_specifications_v1_1
BP3 N/ABP3 is not applicable in this VCEP because these genes are not interpreted using BP3 repetitive-region logic. Details ▾Hide ▴
Rule
Not applicable for this VCEP.
Evidence considered
- Brain Malformations VCEP BP3 applicability statement
Sources
cspec ↗vcep_clingen_brainmalform_acmg_specifications_v1_1
BP4 N/ABP4 is not applicable because this is a missense variant and the VCEP restricts BP4 to synonymous, intronic non-canonical splice, or UTR variants assessed for splicing impact. Computational results were reviewed, including SpliceAI max delta 0.00, REVEL 0.236, and BayesDel -0.391355, but these do not trigger BP4 for this missense change under the VCEP rule. Details ▾Hide ▴
Rule
BP4 applies only to synonymous, intronic non-canonical splice, and UTR variants under this VCEP.
Evidence considered
- Missense consequence p.Ile391Met
- SpliceAI max delta 0.00
- REVEL score 0.236
- BayesDel score -0.391355
Sources
BP7 N/ABP7 is not applicable because this is a missense variant, whereas the VCEP restricts BP7 to synonymous, intronic non-canonical splice, and other non-coding variants. Details ▾Hide ▴
Identifiers
- Gene
- PIK3CA
- Transcript
- NM_006218.2
- Coding (HGVS c.)
- NM_006218.2:c.1173A>G
- Protein (HGVS p.)
- NP_006209.2:p.(Ile391Met)
- GRCh38
- chr3:179209622 A>G
- GRCh37
- chr3:178927410 A>G
Gene diagram
Every interpreted variant in PIK3CA, mapped onto the exon structure of NM_006218.2. Select a row to find it on the plot.
PIK3CANM_006218.2
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 PIK3CA
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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
106,360 / 1,609,518 alleles
AF 0.0661 · 4921 homozygotes · FAF 0.209
gnomAD v2.1
18,372 / 279,610 alleles
AF 0.0657 · 1032 homozygotes · FAF 0.205
By genetic ancestry
gnomAD v4.1
AF 0.066 · 106360 / 1,609,518 alleles · 4921 hom · FAF 0.21
| African/African American15815 / 74,780 | 0.211715 hom |
| Middle Eastern849 / 6,052 | 0.1464 hom |
| Ashkenazi Jewish3823 / 29,530 | 0.13235 hom |
| Amish74 / 912 | 0.0812 hom |
| Remaining individuals4887 / 62,294 | 0.078222 hom |
| European (non-Finnish)73750 / 1,176,896 | 0.0632466 hom |
| Admixed American3717 / 59,832 | 0.062153 hom |
| European (Finnish)1679 / 63,916 | 0.02624 hom |
| South Asian1761 / 90,564 | 0.01940 hom |
| East Asian5 / 44,742 | 0.00011 |
gnomAD v2.1
AF 0.066 · 18372 / 279,610 alleles · 1032 hom · FAF 0.2
| African/African American5097 / 24,124 | 0.21531 hom |
| Ashkenazi Jewish1360 / 10,350 | 0.1385 hom |
| Remaining individuals554 / 7,090 | 0.07827 hom |
| European (non-Finnish)8298 / 128,344 | 0.065299 hom |
| Admixed American1857 / 34,884 | 0.05365 hom |
| European (Finnish)621 / 25,020 | 0.02511 hom |
| South Asian585 / 30,324 | 0.01914 hom |
0 alternate alleles recorded in 1 other group: East Asian.
Statements
gnomAD v4.1
This variant is present in gnomAD v4.1 (AF= 0.0660819; MAF= 6.60819%, 106360/1609518 alleles, homozygotes = 4921) and has highest observed frequency in the African/African American population (AF= 0.211487; MAF= 21.14870%, 15815/74780 alleles, homozygotes = 1715); grpmax FAF= 0.208728.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 0.0657058; MAF= 6.57058%, 18372/279610 alleles, homozygotes = 1032) and has highest observed frequency in the African/African American population (AF= 0.211283; MAF= 21.12834%, 5097/24124 alleles, homozygotes = 531); grpmax FAF= 0.204728.
Other predictors
- REVEL
- Not available
- BayesDel
- Not available
How the predictions were used
PP3 N/APP3 is not applicable in this VCEP for PIK3CA gain-of-function disease mechanisms. Computational results were reviewed, including REVEL 0.236, BayesDel -0.391355, and SpliceAI max delta 0.00, but the specification does not use PP3 for these missense gain-of-function variants. Details ▾Hide ▴
Rule
PP3 is not applicable for this VCEP because traditional prediction algorithms are not used for these GOF variants.
Evidence considered
- REVEL score 0.236
- BayesDel score -0.391355
- SpliceAI max delta 0.00
- VCEP PP3 not applicable for GOF variants
Sources
BP4 N/ABP4 is not applicable because this is a missense variant and the VCEP restricts BP4 to synonymous, intronic non-canonical splice, or UTR variants assessed for splicing impact. Computational results were reviewed, including SpliceAI max delta 0.00, REVEL 0.236, and BayesDel -0.391355, but these do not trigger BP4 for this missense change under the VCEP rule. Details ▾Hide ▴
Rule
BP4 applies only to synonymous, intronic non-canonical splice, and UTR variants under this VCEP.
Evidence considered
- Missense consequence p.Ile391Met
- SpliceAI max delta 0.00
- REVEL score 0.236
- BayesDel score -0.391355
Sources
BP7 N/ABP7 is not applicable because this is a missense variant, whereas the VCEP restricts BP7 to synonymous, intronic non-canonical splice, and other non-coding variants. Details ▾Hide ▴
Statement
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00). REVEL score = 0.236. BayesDel score = -0.391355.
0 paper records listed. No publication is explicitly linked to an applied criterion in the recorded metadata.
Screenshots represent source records captured during evidence collection. Select one to view the recorded source content.
gnomAD v4.1
106,360 / 1,609,518 recorded alleles
Open source ↗
gnomAD v2.1
Captured gnomAD v2.1 source record
Open source ↗
SpliceAI Lookup
Captured SpliceAI source record
Open source ↗
ClinVar
Captured ClinVar source record
Open source ↗
COSMIC
Captured COSMIC source record
Open source ↗
Cancer hotspots
Captured Cancer Hotspots source record
Open source ↗
OncoKB
Captured OncoKB source record
Open source ↗
ClinGen CSpec
Captured ClinGen CSpec source record
Open source ↗
All source links
- ClinGen CSpec ↗cspec.genome.network/cspec/ui/svi/doc/467907148
- ClinVar ↗www.ncbi.nlm.nih.gov/clinvar/variation/135038/
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/3-178927410-A-G?dataset=gnomad_r2_1
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr3-179209622-A-G?dataset=gn…
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_006218.2%3Ac.1173…
- OncoKB ↗www.oncokb.org/gene/PIK3CA/I391M
- COSMIC ↗cancer.sanger.ac.uk/cosmic/mutation/overview?id=108145230
- 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= 0.0660819; MAF= 6.60819%, 106360/1609518 alleles, homozygotes = 4921) and has highest observed frequency in the African/African American population (AF= 0.211487; MAF= 21.14870%, 15815/74780 alleles, homozygotes = 1715); grpmax FAF= 0.208728.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 0.0657058; MAF= 6.57058%, 18372/279610 alleles, homozygotes = 1032) and has highest observed frequency in the African/African American population (AF= 0.211283; MAF= 21.12834%, 5097/24124 alleles, homozygotes = 531); grpmax FAF= 0.204728.
ClinVar
This variant has been reported in ClinVar as Benign (7 clinical laboratories) and as Benign by ClinGen Brain Malformations Variant Curation Expert Panel (expert panel).
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00). REVEL score = 0.236. BayesDel score = -0.391355.
Functional
OncoKB identified variant-specific curated literature and context relevant to functional review; biological-effect context: Inconclusive; curated oncogenicity label: Inconclusive.
Somatic
This variant does not lie in a statistically significant hotspot. This variant has previously been reported in somatic cancers (COSMIC; COSV55885079, n = 104 times).
Cancer Hotspots
This variant does not lie in a statistically significant hotspot.