Classification rationale

BA1BS1BP4BP7 Benign

WT1 c.1107A>G

The WT1 c.1107A>G (p.Arg369=) variant has been reported in ClinVar as benign.¹ This variant is common in population databases, with an allele frequency of 0.235708 in gnomAD v2.1 and 0.180386 in gnomAD v4.1, which is far above benign population thresholds.² In silico evidence supports a benign interpretation because this synonymous change does not alter the encoded amino acid and SpliceAI predicts no significant splice impact with a maximum delta score of 0.01.³

BA1 + BS1 + BP4 + BP7 → Benign

1 clinvar ↗

2 gnomad_v2 ↗gnomad_v4 ↗

3 spliceai ↗

Gene diagram · NM_024426.4 · variants mapped to exon structure

WT1 NM_024426.4

Fetching transcript structure from UCSC…

Applied criteria · 4 met · select any tile

Met

Not met

Not assessed

N/A

Strength very strong supporting

Pathogenic evidence

PVS

PS

PM

PP

Benign evidence

BA

BS

BP

—

Rationale

Select a criterion.

Sources

Evidence used

Gaps remaining

Rule

—

Research & evidence

Population frequency · supports benign

gnomAD v4.1

gnomAD v2.1

v4.1

This variant is present in gnomAD v4.1 (AF= 0.180386; MAF= 18.03862%, 291078/1613638 alleles, homozygotes = 35597) and has highest observed frequency in the East Asian population (AF= 0.671155; MAF= 67.11547%, 30108/44860 alleles, homozygotes = 10092); grpmax FAF= 0.664805.

v2.1

This variant is present in gnomAD v2.1 (AF= 0.235708; MAF= 23.57076%, 66569/282422 alleles, homozygotes = 11532) and has highest observed frequency in the East Asian population (AF= 0.697872; MAF= 69.78717%, 13903/19922 alleles, homozygotes = 4884); grpmax FAF= 0.685973.

Allele frequency by ancestry

three datasets · side by side

gnomAD v4.1

18% · 291078 / 1,613,638
35597 hom · FAF 66%

East Asian 30108 / 44,860	67% 10092 hom
South Asian 32191 / 91,058	35% 5879 hom
Admixed American 20521 / 59,984	34% 3749 hom
Remaining individuals 12655 / 62,492	20% 1606 hom
Amish 179 / 910	20% 23 hom
Middle Eastern 1124 / 5,992	19% 117 hom
Ashkenazi Jewish 5273 / 29,608	18% 452 hom
European (Finnish) 10979 / 63,800	17% 959 hom
European (non-Finnish) 169781 / 1,179,968	14% 12283 hom
African/African American 8267 / 74,966	11% 437 hom

gnomAD v2.1

24% · 66569 / 282,422
11532 hom · FAF 69%

East Asian 13903 / 19,922	70% 4884 hom
Admixed American 13014 / 35,402	37% 2537 hom
South Asian 10896 / 30,608	36% 1975 hom
Remaining individuals 1419 / 7,212	20% 140 hom
Ashkenazi Jewish 1832 / 10,368	18% 156 hom
European (Finnish) 4363 / 24,938	17% 363 hom
European (non-Finnish) 18363 / 129,014	14% 1329 hom
African/African American 2779 / 24,958	11% 148 hom

gnomAD v4 ↗ gnomAD v2 ↗

ClinVar

This variant has been reported in ClinVar as Benign (20 clinical laboratories) and as benign (1 clinical laboratory).

ClinVar ↗

In silico

SpliceAI predicts no significant splice impact for this variant (max delta score = 0.01).

SpliceAI ↗

Functional Unknown Oncogenic Effect

OncoKB oncogenicity for this specific variant: Unknown Oncogenic Effect (variant has not been individually curated).

OncoKB ↗

COSMIC

Cancer hotspots

Somatic evidence Not in COSMIC / hotspots

COSMIC

This variant does not lie in a statistically significant hotspot. This variant has previously been reported in somatic cancers (COSMIC; COSV60066333, n = 111 times).

Hotspots

This variant does not lie in a statistically significant hotspot.

COSMIC ↗ Hotspots ↗

Sources & reference links

7Sources

ClinVar

gnomAD v2.1

gnomAD v4.1

SpliceAI

OncoKB

COSMIC

Cancer hotspots