About SF3B1
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
SF3B1 c.1874G>T, p.(Arg625Leu)
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: 4
Benign evidence criteria: 0
Pathogenic criteria applied · 4
PS3Supporting
PS3 · supporting
The variant p.Arg625Leu was detected in uveal melanoma and MDS tumors and is associated with aberrant alternative splicing. The SF3B1 R625 codon is a recurrent hotspot where mutations induce neomorphic cryptic 3' splice site selection. The variant was explicitly identified in patient tumors exhibiting the alternative splicing signature (PMID:23861464, PMID:24434863). Mechanistic studies (PMID:26565915) experimentally demonstrated that hotspot mutations in the HEAT domain (residues 622-781) cause aberrant splicing through altered branch point usage, and the authors concluded that functional consequences are similar across hotspot mutations. However, R625L was not directly tested in a controlled experimental system (minigene assay, overexpression, or knockdown rescue), limiting the strength to supporting.
PM1Moderate
PM1 · moderate
The variant alters Arg625, located within the HEAT domain (H4-H8 repeats, residues 622-781) of SF3B1. This is a well-characterized critical functional domain required for branch point sequence recognition and pre-mRNA splicing. Residue R625 is a statistically significant hotspot in cancer (CancerHotspots.org) and is the most frequently mutated codon in uveal melanoma (PMID:23861464). Mutations in this domain have been experimentally shown to induce neomorphic aberrant splicing activity (PMID:26565915).
PM2Supporting
PM2 · supporting
The variant is absent from gnomAD v2.1 (exomes) and v4.1 (0/1,614,004 alleles, AF=0.0%), meeting the PM2 threshold of <0.1% allele frequency in population databases for a gene without a CSPEC framework.
PP3Supporting
PP3 · supporting
REVEL score of 0.865 predicts a deleterious effect on protein function. BayesDel score of 0.3522 is inconclusive. SpliceAI predicts no significant splice impact (max delta score 0.17). While only one of three in silico tools strongly supports pathogenicity, the high REVEL score in a well-conserved functional domain supports a deleterious effect.
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: PS3 supporting, PM1 moderate, PM2 supporting, PP3 supporting; combination = 1 moderate + 3 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
0 / 1,614,004 alleles
gnomAD v4.1: 0 / 1,614,004 alleles. Recorded AF 0. Recorded homozygote count 0.
gnomAD v2.1
Absent from gnomAD v2.1.
gnomAD-Canada
Not available in gnomAD-Canada v1.0.
SpliceAI score
0.170 maximum delta
Recorded SpliceAI maximum delta score: 0.170. Refer to the recorded PP3/BP4 rationale for interpretation.
ClinVar submissions
Not recorded
A ClinVar laboratory submission summary was not recorded.
Context only
ClinVar ↗
Functional evidence
Statement recorded
OncoKB identified variant-specific curated literature and context relevant to functional review; curated oncogenicity label: Likely Oncogenic.
COSMIC
Cancer Hotspots
Somatic evidence
40 recorded samples
This variant has previously been reported in somatic cancers (COSMIC; COSV59206122, n = 40 times).
Cancer Hotspots
This variant lies 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.
26 criteria with recorded statuses: 4 met · 20 not met · 0 not assessed · 2 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.
Met
Not met
Not assessed
Not applicable
One moderate pathogenic criterion (PM1) and three supporting pathogenic criteria (PM2, PS3, PP3) are met.
Under generic ACMG/AMP 2015 combination rules (PMID:25741868), the combination of 1 moderate and 3 supporting pathogenic criteria is insufficient to reach Likely Pathogenic (requires ≥1 Moderate + ≥4 Supporting, ≥2 Moderate + ≥2 Supporting, or other qualifying combinations).
No benign criteria are met.
Final classification: Variant of Uncertain Significance (VUS).
No criteria match.
Met · 4
PS3 SupportingThe variant p.Arg625Leu was detected in uveal melanoma and MDS tumors and is associated with aberrant alternative splicing. The SF3B1 R625 codon is a recurrent hotspot where mutations induce neomorphic cryptic 3' splice site selection. The variant was explicitly identified in patient tumors exhibiting the alternative splicing signature (PMID:23861464, PMID:24434863). Mechanistic studies (PMID:26565915) experimentally demonstrated that hotspot mutations in the HEAT domain (residues 622-781) cause aberrant splicing through altered branch point usage, and the authors concluded that functional consequences are similar across hotspot mutations. However, R625L was not directly tested in a controlled experimental system (minigene assay, overexpression, or knockdown rescue), limiting the strength to supporting. Details ▾Hide ▴
Evidence considered
- PMID:23861464: R625L detected in 1/105 uveal melanomas
- SF3B1-mutant tumors showed alternative splicing of CRNDE
- ABCC5
- UQCC and other genes by microarray
- RNA-seq
- and qRT-PCR.
- PMID:24434863: R625L/H/D/C mutations in MDS samples clustered with the common alternative splicing signature shared across uveal melanoma
- MDS
- and CLL.
- PMID:26565915: Experimental demonstration that SF3B1 hotspot mutations (K700E
- K666N
- H662Q) induce neomorphic cryptic 3' splice site selection through use of a different branch point
- authors state functional consequences are similar across all hotspot mutations in the HEAT domain.
Still missing
- No direct experimental functional testing of the R625L variant in a controlled system (e.g.
- minigene splicing assay
- complementation assay).
Sources
PM1 ModerateThe variant alters Arg625, located within the HEAT domain (H4-H8 repeats, residues 622-781) of SF3B1. This is a well-characterized critical functional domain required for branch point sequence recognition and pre-mRNA splicing. Residue R625 is a statistically significant hotspot in cancer (CancerHotspots.org) and is the most frequently mutated codon in uveal melanoma (PMID:23861464). Mutations in this domain have been experimentally shown to induce neomorphic aberrant splicing activity (PMID:26565915). Details ▾Hide ▴
Evidence considered
- Residue R625 is in the HEAT domain (H4-H8 repeats)
- a critical functional domain for branch point sequence recognition.
- Statistically significant hotspot at cancerhotspots.org.
- PMID:23861464: R625 is the predominant SF3B1 mutation hotspot in uveal melanoma.
- PMID:26565915: Hotspot mutations in the HEAT domain (residues 622-781) cause neomorphic aberrant 3' splice site selection.
Sources
PM2 SupportingThe variant is absent from gnomAD v2.1 (exomes) and v4.1 (0/1,614,004 alleles, AF=0.0%), meeting the PM2 threshold of <0.1% allele frequency in population databases for a gene without a CSPEC framework. Details ▾Hide ▴
Evidence considered
- gnomAD v2.1: absent.
- gnomAD v4.1: 0/1
- 614
- 004 alleles (AF=0.0%)
- including 0/75
- 014 African/African American alleles.
Sources
PP3 SupportingREVEL score of 0.865 predicts a deleterious effect on protein function. BayesDel score of 0.3522 is inconclusive. SpliceAI predicts no significant splice impact (max delta score 0.17). While only one of three in silico tools strongly supports pathogenicity, the high REVEL score in a well-conserved functional domain supports a deleterious effect. Details ▾Hide ▴
Evidence considered
- REVEL: 0.865 (deleterious).
- BayesDel: 0.3522 (inconclusive).
- SpliceAI: max delta 0.17 (no predicted splice impact
- DS_AG=0.03
- DS_AL=0.00
- DS_DG=0.17
- DS_DL=0.04).
Still missing
- HCI prior score not available for SF3B1.
Sources
Not met · 20 · evaluated, threshold not reached
PS1 No alternative nucleotide change at position c.1874 resulting in the same amino acid substitution (p.Arg625Leu) has been identified. Details ▾Hide ▴
Evidence considered
- No same-amino-acid
- different-nucleotide comparator identified.
PS2 No de novo observation of NM_012433.3:c.1874G>T has been reported. De novo SF3B1 variants described in neurodevelopmental disorders (PMID:41577671) are largely distinct from cancer-associated hotspot variants such as R625L. Details ▾Hide ▴
Evidence considered
- PMID:41577671 describes de novo germline SF3B1 variants but R625L is not among them.
Still missing
- No de novo testing data available for this specific variant.
PS4 No germline case-control data are available to demonstrate statistically significant enrichment of this variant in affected individuals. The variant has been observed in somatic cancers (COSMIC n=40, one uveal melanoma in PMID:23861464) but this does not satisfy PS4 which requires germline disease association. Details ▾Hide ▴
Evidence considered
- COSMIC: n=40 somatic occurrences. PMID:23861464: 1 uveal melanoma case.
Still missing
- No germline case-control or cohort enrichment data available.
PM5 No pathogenic missense variant at the same amino acid position (Arg625) has been identified in ClinVar for PM5 comparator analysis. The automated PM5 candidate search returned no candidates. Details ▾Hide ▴
Evidence considered
- PM5 candidate search: 0 same-residue candidate variants found in ClinVar.
Still missing
- No ClinVar entries at this residue to serve as PM5 comparators.
Sources
pm5_candidates
PM6 No de novo observation of this variant has been reported. De novo SF3B1 variants reported in neurodevelopmental disorders (PMID:41577671) are distinct from cancer-associated hotspot mutations. Details ▾Hide ▴
Evidence considered
- No de novo report for NM_012433.3:c.1874G>T in the literature.
Still missing
- No parental testing or de novo analysis data.
PP1 No segregation data are available for this variant in affected families. Details ▾Hide ▴
Evidence considered
- No family segregation studies identified.
Still missing
- No cosegregation data.
PP2 SF3B1 germline disease mechanisms are still emerging. While missense variants are a known mechanism in somatic cancer (neomorphic gain-of-function), the germline disease spectrum includes both predicted loss-of-function and missense variants with distinct functional consequences (PMID:41577671). A low rate of benign missense variation has not been specifically established for germline SF3B1. Details ▾Hide ▴
Evidence considered
- PMID:41577671: Both pLoF and missense variants found in SF3B1-related neurodevelopmental disorder
- missense variants are gain-of-function
- not loss-of-function.
Still missing
- Gene-level constraint metrics for germline SF3B1 missense variation not established.
PP4 No specific patient phenotype information is available for germline assessment of this variant. The variant has been observed in somatic cancer contexts (uveal melanoma, MDS) but no germline phenotype data are provided. Details ▾Hide ▴
Evidence considered
- No germline phenotype data available.
Still missing
- No germline phenotype or clinical history provided.
PP5 No reputable germline source has classified this variant as pathogenic. It is absent from ClinVar. OncoKB classifies it as 'Likely Oncogenic' in a somatic context, which does not satisfy PP5 for germline assessment. Details ▾Hide ▴
Evidence considered
- ClinVar: absent. OncoKB: Likely Oncogenic (somatic only).
BA1 The variant is absent from gnomAD v4.1 (0/1,614,004 alleles, AF=0.0%), far below the BA1 threshold of >1%. Details ▾Hide ▴
BS1 The variant is absent from gnomAD (AF=0.0%), far below the BS1 threshold of >0.3% allele frequency. Details ▾Hide ▴
BS2 The variant is absent from gnomAD. No observation in healthy adults has been documented to support a benign role. Details ▾Hide ▴
Evidence considered
- Absent from all population databases.
BS3 Functional studies demonstrate that SF3B1 hotspot mutations in the HEAT domain, including at codon R625, induce neomorphic gain-of-function activity (aberrant cryptic 3' splice site selection, altered branch point usage) rather than having no deleterious effect. These findings are not consistent with a benign functional impact. Details ▾Hide ▴
Evidence considered
- PMID:23861464: SF3B1 mutations at codon R625 associated with aberrant alternative splicing in uveal melanoma.
- PMID:26565915: SF3B1 hotspot mutations cause neomorphic gain-of-function splicing defects.
Sources
BS4 No segregation data are available to demonstrate lack of cosegregation with disease. Details ▾Hide ▴
Evidence considered
- No family studies available.
Still missing
- No cosegregation data.
BP1 SF3B1-related disease is not caused primarily by truncating variants. Both predicted loss-of-function and missense variants are reported in the germline neurodevelopmental disorder spectrum (PMID:41577671), and missense variants in the HEAT domain are the predominant pathogenic mechanism in somatic disease. Details ▾Hide ▴
Evidence considered
- PMID:41577671: Both pLoF (n=9) and missense (n=17) variants found in SF3B1-related neurodevelopmental disorder.
BP2 No observation of this variant in trans with a known pathogenic variant has been reported. Details ▾Hide ▴
Evidence considered
- No trans configuration data available.
BP4 Computational evidence does not support a benign impact. REVEL score of 0.865 predicts a deleterious effect, and the variant is located in a highly constrained functional domain. Details ▾Hide ▴
Evidence considered
- REVEL: 0.865 (deleterious
- not benign).
- SpliceAI: max delta 0.17 (no predicted splice impact but does not indicate benign effect).
Sources
revelspliceai ↗
BP5 No alternative molecular basis for disease has been identified in a case harboring this variant. Details ▾Hide ▴
Evidence considered
- No alternative genetic cause identified.
BP6 No reputable source has classified this variant as benign. The variant is absent from ClinVar. Details ▾Hide ▴
Evidence considered
- ClinVar: absent. No benign classification from any source.
PS5 No alternative pathogenic variant at the same nucleotide position (c.1874) with functional data has been identified in ClinVar or the literature. Details ▾Hide ▴
Evidence considered
- No comparator variant at c.1874 identified.
Not applicable · 2· recorded as not applicable Show reasons ▾Hide reasons ▴
PVS1 N/AThis is a missense variant (p.Arg625Leu). PVS1 under the generic ClinGen SVI framework (PMC6185798) applies only to null variants (nonsense, frameshift, canonical ±1,2 splice consensus variants). The variant does not fall into any PVS1 null-variant bucket. Details ▾Hide ▴
Evidence considered
- Missense substitution at c.1874G>T
- no PVS1 null-variant criteria satisfied.
Sources
pvs1_variant_assessmentpvs1_generic_framework ↗
BP7 N/ABP7 applies only to synonymous (silent) variants. NM_012433.3:c.1874G>T is a missense variant (p.Arg625Leu). Details ▾Hide ▴
Evidence considered
- Missense substitution
- not synonymous.
Identifiers
- Gene
- SF3B1
- Transcript
- NM_012433.3
- Coding (HGVS c.)
- NM_012433.3:c.1874G>T
- Protein (HGVS p.)
- NP_036565.2:p.(Arg625Leu)
- GRCh38
- chr2:197402759 C>A
- GRCh37
- chr2:198267483 C>A
- COSMIC
- COSV59206122
Gene diagram
Every interpreted variant in SF3B1, mapped onto the exon structure of NM_012433.3. Select a row to find it on the plot.
SF3B1NM_012433.3
Fetching transcript structure from UCSC…
Exons
—
Transcript span
—
Strand
—
Variants mapped
—
Source
UCSC ncbiRefSeqCurated
All variants in SF3B1
—
Select a row to find it on the plot; use the link to open its page.
| Protein | Location | Classification | Link |
|---|
gnomAD v4.1
0 / 1,614,004 alleles
AF 0 · 0 homozygotes
gnomAD v2.1
Allele count data not recorded
gnomAD-Canada v1.0
Allele count data not recorded
By genetic ancestry
gnomAD v4.1
AF 0 · 0 / 1,614,004 alleles · 0 hom
No alternate alleles recorded in the displayed ancestry groups.
Statements
gnomAD v4.1
This variant is present in gnomAD v4.1 (AF= 0; MAF= 0.00000%, 0/1614004 alleles, homozygotes = 0) and has highest observed frequency in the African/African American population (AF= 0; MAF= 0.00000%, 0/75014 alleles, homozygotes = 0).
gnomAD v2.1
Absent from gnomAD v2.1.
gnomAD-Canada
Not available in gnomAD-Canada v1.0.
SpliceAI and Pangolin
Other predictors
- REVEL
- 0.865
- BayesDel
- 0.352
How the predictions were used
PP3 SupportingREVEL score of 0.865 predicts a deleterious effect on protein function. BayesDel score of 0.3522 is inconclusive. SpliceAI predicts no significant splice impact (max delta score 0.17). While only one of three in silico tools strongly supports pathogenicity, the high REVEL score in a well-conserved functional domain supports a deleterious effect. Details ▾Hide ▴
Evidence considered
- REVEL: 0.865 (deleterious).
- BayesDel: 0.3522 (inconclusive).
- SpliceAI: max delta 0.17 (no predicted splice impact
- DS_AG=0.03
- DS_AL=0.00
- DS_DG=0.17
- DS_DL=0.04).
Still missing
- HCI prior score not available for SF3B1.
Sources
BP4 Computational evidence does not support a benign impact. REVEL score of 0.865 predicts a deleterious effect, and the variant is located in a highly constrained functional domain. Details ▾Hide ▴
Evidence considered
- REVEL: 0.865 (deleterious
- not benign).
- SpliceAI: max delta 0.17 (no predicted splice impact but does not indicate benign effect).
Sources
revelspliceai ↗
BP7 N/ABP7 applies only to synonymous (silent) variants. NM_012433.3:c.1874G>T is a missense variant (p.Arg625Leu). Details ▾Hide ▴
Evidence considered
- Missense substitution
- not synonymous.
Statement
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.17). REVEL score = 0.865. BayesDel score = 0.3522.
4 paper records listed. 3 cited in the classification.
Cited in the classification
-
PMID 23861464 ↗SF3B1 mutations are associated with alternative splicing in uveal melanoma.Identified p.Arg625Leu (R625L) in 1 of 105 uveal melanoma tumor samples in the validation cohort. SF3B1-mutant tumors, including those with codon R625 mutations, demonstrated aberrant alternative splicing affecting CRNDE, ABCC5, UQCC, and five other genes, validated by microarray, RNA-seq, and qRT-PCR.→ PS3 → PM1 Names this variant
Source detail
We screened SF3B1 in 105 additional consecutive archival primary uveal melanomas and detected 15 additional mutations (8 p.R625H, 4 p.R625C, 1 p.R625P, 1 p.R625L, 1 p.K666T; Supplementary Table 7).
Location Results section: 'We screened SF3B1 in 105 additional consecutive archival primary uveal melanomas and detected 15 additional mutations (8 p.R625H, 4 p.R625C, 1 p.R625P, 1 p.R625L, 1 p.K666T; Supplementary Table 7).'
Context Patient tumor samples (primary uveal melanoma); Affymetrix HTA2.0 microarrays, RNA-seq, and qRT-PCR for splicing analysis
-
PMID 24434863 ↗A common alternative splicing signature is associated with SF3B1 mutations in malignancies from different cell lineages.R625L listed among SF3B1-mutant MDS samples (4 MDS cases with R625L/H/D/C). All SF3B1-mutated samples, including R625-mutant tumors, clustered together by splicing signature, confirming a common alternative splicing pattern across uveal melanoma, MDS, and CLL.→ PS3 Names this variant
Source detail
24 MDS SF3B1 mutated samples cases [K700E (14), H622Q (4), D781G (2), R625L/H/D/C (4)] and 19 SF3B1 mutated UM samples [K625H/C/L/P (16), K666M/T (2), D700E (1)].
Location Results section: '24 MDS SF3B1 mutated samples cases [K700E (14), H622Q (4), D781G (2), R625L/H/D/C (4)] and 19 SF3B1 mutated UM samples [K625H/C/L/P (16)]...'
Context Patient tumor samples; RT-QPCR splicing analysis of UQCC, CRNDE, ANKHD1, GUSBP1, ABCC5 across 161 tumors
-
PMID 26565915 ↗Cancer-Associated SF3B1 Hotspot Mutations Induce Cryptic 3' Splice Site Selection through Use of a Different Branch Point.Experimentally demonstrated that SF3B1 hotspot mutations in the HEAT domain (residues 622-781) induce neomorphic cryptic 3' splice site selection through use of a different branch point. The study tested K700E, K666N, and H662Q experimentally and concluded that all hotspot mutations share similar functional consequences. R625L was not directly tested.→ PS3 → PM1 Does not name this variant
Source detail
all hotspot mutations are co-localized in a limited, positively charged region even though they are distributed across five different HEAT domains... our data suggest the functional consequences on splicing for these changes are similar.
Location Introduction: 'The recurrent hotspot mutations in SF3B1 are found exclusively in the C-terminal HEAT domains (residues 622-781).' Discussion: 'all hotspot mutations are co-localized in a limited, positively charged region...our data suggest the functional consequences on splicing for these changes are similar.'
Context Nalm-6 isogenic cell lines, K562 cells, 293FT cells; RNA-seq, Nanostring, minigene splicing assays, lariat PCR, SILAC proteomics
Other recorded publications
-
PMID 33031100 ↗Mutant SF3B1 promotes AKT- and NF-κB-driven mammary tumorigenesis.Describes mutant SF3B1 promoting AKT- and NF-κB-driven mammary tumorigenesis. The abstract discusses SF3B1 hotspot mutations in breast cancer at the gene level. The specific variant NM_012433.3:c.1874G>T (p.Arg625Leu) was not identified in the available abstract.Does not name this variant
Screenshots represent source records captured during evidence collection. Select one to view the recorded source content.
gnomAD v4.1
0 / 1,614,004 recorded alleles
Open source ↗
gnomAD v2.1
Captured gnomAD v2.1 source record
Open source ↗
SpliceAI Lookup
Recorded maximum delta 0.170
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 ↗
All source links
- ClinVar ↗www.ncbi.nlm.nih.gov/clinvar/?term=NM_012433.3%3Ac.1874G%3ET
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/2-198267483-C-A?dataset=gnomad_r2_1
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr2-197402759-C-A?dataset=gn…
- gnomAD-Canada ↗http://192.168.4.76:8001/variant/2-197402759-C-A
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_012433.3%3Ac.1874…
- OncoKB ↗www.oncokb.org/gene/SF3B1/R625L
- COSMIC ↗cancer.sanger.ac.uk/cosmic/mutation/overview?id=126501074
- 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; MAF= 0.00000%, 0/1614004 alleles, homozygotes = 0) and has highest observed frequency in the African/African American population (AF= 0; MAF= 0.00000%, 0/75014 alleles, homozygotes = 0).
gnomAD v2.1
Absent from gnomAD v2.1.
gnomAD-Canada
Not available in gnomAD-Canada v1.0.
ClinVar
This variant is absent from ClinVar.
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.17). REVEL score = 0.865. BayesDel score = 0.3522.
Functional
OncoKB identified variant-specific curated literature and context relevant to functional review; curated oncogenicity label: Likely Oncogenic.
Somatic
This variant lies in a statistically significant hotspot. This variant has previously been reported in somatic cancers (COSMIC; COSV59206122, n = 40 times).
Cancer Hotspots
This variant lies in a statistically significant hotspot.