WT1c.1107A>GBenign

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Variant interpretation report

WT1 c.1107A>G, p.(Arg369=)

NM_024426.4:c.1107A>G NP_077744.3:p.(Arg369=) View identifiers

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.

About WT1

No gene-level summary was recorded for this case.

Key facts

Evidence used: 1 stand alone (benign) · 1 strong (benign) · 2 supporting (benign)
Expert rules: Not recorded

Evidence considered

View criteria

Applied evidence criteria

BA1 (stand alone): Population frequency is well above the benign stand-alone threshold of 0.01. This variant is present in gnomAD v2.1 at AF 0.235708 and in gnomAD v4.1 at AF 0.180386, with East Asian frequencies of 0.697872 and 0.671155, respectively.
BS1 (strong): Population frequency is above the strong benign threshold of 0.003. This variant is present in gnomAD v2.1 at AF 0.235708 and in gnomAD v4.1 at AF 0.180386, both greatly exceeding that threshold.
BP4 (supporting): Available computational evidence supports no impact on the gene product or splicing. The variant is synonymous, p.(Arg369=), and SpliceAI predicts no significant splice impact with a maximum delta score of 0.01.
BP7 (supporting): This is a synonymous variant, WT1 c.1107A>G (p.Arg369=), and SpliceAI predicts no significant splice impact with a maximum delta score of 0.01, supporting no effect on RNA splicing.

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: 0 Benign evidence criteria: 4

Pathogenic criteria applied · 0

No pathogenic criterion marked as applied in the recorded assessment.

Benign criteria applied · 4

BA1Stand alone

BA1 · stand alone

Population frequency is well above the benign stand-alone threshold of 0.01. This variant is present in gnomAD v2.1 at AF 0.235708 and in gnomAD v4.1 at AF 0.180386, with East Asian frequencies of 0.697872 and 0.671155, respectively.

BS1Strong

BS1 · strong

Population frequency is above the strong benign threshold of 0.003. This variant is present in gnomAD v2.1 at AF 0.235708 and in gnomAD v4.1 at AF 0.180386, both greatly exceeding that threshold.

BP4Supporting

BP4 · supporting

Available computational evidence supports no impact on the gene product or splicing. The variant is synonymous, p.(Arg369=), and SpliceAI predicts no significant splice impact with a maximum delta score of 0.01.

BP7Supporting

BP7 · supporting

This is a synonymous variant, WT1 c.1107A>G (p.Arg369=), and SpliceAI predicts no significant splice impact with a maximum delta score of 0.01, supporting no effect on RNA splicing.

Recorded classification: Benign

gene-specific framework lacked a usable explicit final combination framework, so generic ACMG/AMP 2015 final-combination rules were applied as fallback.

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

291,078 / 1,613,638 alleles

gnomAD v4.1: 291,078 / 1,613,638 alleles. Recorded AF 0.180386. Recorded homozygote count 35597.

gnomAD 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.

Applied · BA1, BS1 →

gnomAD v4.1 ↗gnomAD v2.1 ↗

No screenshot for this evidence

Computational predictions

Not recorded

No SpliceAI or REVEL score is recorded in the fields used for this tile.

Applied · BP4, BP7 →

ClinVar submissions

Not recorded

A ClinVar laboratory submission summary was not recorded.

Context only ClinVar ↗

Functional evidence

Statement recorded

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

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

COSMIC ↗Cancer Hotspots ↗

For specialists

Technical detail

ACMG/AMP criteria under Not recorded, with the data and sources behind each one.

28 criteria with recorded statuses: 4 met · 5 not met · 13 not assessed · 6 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.

Pathogenic

PVS1 PS1 PS2 PS3 PS4 PM1 PM2 PM3 PM4 PM5 PM6 PP1 PP2 PP3 PP4 PP5

Benign

BA1 BS1 BS2 BS3 BS4 BP1 BP2 BP3 BP4 BP5 BP6 BP7

Met Not met Not assessed Not applicable

The WT1 c.1107A>G (p.Arg369=) variant has been reported in ClinVar as benign.

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.

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.

Met · 4

BA1 Stand alonePopulation frequency is well above the benign stand-alone threshold of 0.01. This variant is present in gnomAD v2.1 at AF 0.235708 and in gnomAD v4.1 at AF 0.180386, with East Asian frequencies of 0.697872 and 0.671155, respectively. Details ▾Hide ▴

Evidence considered

gnomAD v2.1 AF 0.235708
East Asian AF 0.697872
gnomAD v4.1 AF 0.180386
East Asian AF 0.671155

Sources

gnomad_v2 ↗gnomad_v4 ↗

BS1 StrongPopulation frequency is above the strong benign threshold of 0.003. This variant is present in gnomAD v2.1 at AF 0.235708 and in gnomAD v4.1 at AF 0.180386, both greatly exceeding that threshold. Details ▾Hide ▴

Evidence considered

gnomAD v2.1 AF 0.235708
gnomAD v4.1 AF 0.180386

Sources

gnomad_v2 ↗gnomad_v4 ↗

BP4 SupportingAvailable computational evidence supports no impact on the gene product or splicing. The variant is synonymous, p.(Arg369=), and SpliceAI predicts no significant splice impact with a maximum delta score of 0.01. Details ▾Hide ▴

Evidence considered

synonymous protein prediction p.(Arg369=)
SpliceAI max delta score 0.01

Sources

spliceai ↗

BP7 SupportingThis is a synonymous variant, WT1 c.1107A>G (p.Arg369=), and SpliceAI predicts no significant splice impact with a maximum delta score of 0.01, supporting no effect on RNA splicing. Details ▾Hide ▴

Evidence considered

synonymous protein prediction p.(Arg369=)
SpliceAI max delta score 0.01

Sources

spliceai ↗

Not met · 5 · evaluated, threshold not reached

PVS1 This variant is a synonymous change, WT1 c.1107A>G (p.Arg369=), and does not fall within the generic PVS1 null-variant categories for nonsense, frameshift, or canonical +/-1 or 2 splice-site variants. Details ▾Hide ▴

Evidence considered

WT1 loss of function is an established disease mechanism
the variant is not a generic PVS1-type null variant

Sources

pvs1_gene_contextpvs1_variant_assessmentpvs1_generic_framework ↗

PS4 Available evidence does not show that this variant is enriched in individuals with WT1-related germline disease compared with controls. A ClinVar benign classification and very high population frequency argue against pathogenic case enrichment. Details ▾Hide ▴

Evidence considered

ClinVar benign assertion
very high population frequency in gnomAD

Sources

clinvar ↗gnomad_v2 ↗gnomad_v4 ↗

PM1 This variant does not lie in a statistically significant hotspot, so available evidence does not support location in a critical mutational hot spot or well-established functional domain without benign variation. Details ▾Hide ▴

Evidence considered

Cancer Hotspots did not identify a hotspot row for WT1 Arg369

Sources

hotspots ↗

PM2 This variant is not absent from population databases. In gnomAD v2.1 the overall allele frequency is 0.235708 and in gnomAD v4.1 it is 0.180386, both far above the usual rarity threshold of 0.001 for PM2. Details ▾Hide ▴

Evidence considered

gnomAD v2.1 AF 0.235708
gnomAD v4.1 AF 0.180386

Sources

gnomad_v2 ↗gnomad_v4 ↗

PP3 Available computational evidence does not support a deleterious effect. SpliceAI predicts no significant splice impact with a maximum delta score of 0.01, which is below commonly used splice-impact thresholds. Details ▾Hide ▴

Evidence considered

SpliceAI max delta score 0.01

Sources

spliceai ↗

Not assessed · 13 · no assessment recorded

PS2 No confirmed de novo data with established maternity and paternity were identified for this variant. Details ▾Hide ▴

Still missing

confirmed parental testing

PS3 No well-established functional studies demonstrating a damaging effect of this specific variant were identified. Details ▾Hide ▴

Still missing

variant-specific functional assay data

PM3 No data were identified showing this variant in trans with a pathogenic variant in a recessive disorder. Details ▾Hide ▴

Still missing

phase data in a recessive disease context

PM6 No assumed de novo occurrence data were identified for this variant. Details ▾Hide ▴

Still missing

de novo occurrence data

PP1 No segregation data were identified showing this variant tracking with disease in affected family members. Details ▾Hide ▴

Still missing

family segregation data

PP4 No individual-level phenotype data were identified to show a WT1-related clinical presentation that is highly specific for disease caused by this variant. Details ▾Hide ▴

Still missing

case-level phenotype information

PP5 An external clinical database classification was identified, but this criterion was not used as stand-alone evidence for pathogenicity. Details ▾Hide ▴

Evidence considered

ClinVar classification available

Sources

clinvar ↗

BS2 The variant is observed many times in population databases, including numerous homozygotes, but phenotype-confirmed healthy adult observations were not identified for formal BS2 application. Details ▾Hide ▴

Evidence considered

11
532 homozygotes in gnomAD v2.1
35
597 homozygotes in gnomAD v4.1

Still missing

phenotype-confirmed healthy carrier data

Sources

gnomad_v2 ↗gnomad_v4 ↗

BS3 No well-established functional studies showing a benign effect of this specific variant were identified. Details ▾Hide ▴

Still missing

variant-specific benign functional assay data

BS4 No family data were identified showing lack of segregation with disease. Details ▾Hide ▴

Still missing

nonsegregation data

BP2 No phase data were identified showing this variant in trans with a pathogenic variant for a dominant disorder or in cis with a pathogenic variant. Details ▾Hide ▴

Still missing

phase data

BP5 No evidence was identified for an alternate molecular explanation that would account for the observed phenotype independently of this variant. Details ▾Hide ▴

Still missing

case-level alternate diagnosis data

BP6 An external clinical database classification was identified, but this criterion was not used as stand-alone evidence for benignity. Details ▾Hide ▴

Evidence considered

ClinVar benign classification available

Sources

clinvar ↗

Not applicable · 6· recorded as not applicable Show reasons ▾Hide reasons ▴

PS1 N/AThis criterion applies to a different nucleotide change that produces the same amino acid substitution as a known pathogenic variant. This variant is synonymous and no amino acid substitution is produced. Details ▾Hide ▴

Evidence considered

predicted protein consequence is p.(Arg369=)

PM4 N/AThis criterion applies to protein length changes from in-frame deletions or insertions or stop-loss variants. This variant is synonymous and does not alter protein length. Details ▾Hide ▴

Evidence considered

predicted protein consequence is p.(Arg369=)

PM5 N/AThis criterion applies to a novel missense change at a residue where a different pathogenic missense change has been established. This variant is synonymous and not a missense change. Details ▾Hide ▴

Evidence considered

predicted protein consequence is p.(Arg369=)

PP2 N/AThis criterion applies to missense variants in genes with a low rate of benign missense variation and where missense is a common disease mechanism. This variant is synonymous, not missense. Details ▾Hide ▴

Evidence considered

predicted protein consequence is p.(Arg369=)

BP1 N/AThis criterion applies to missense variants in genes where truncating variants are primarily pathogenic. This variant is synonymous and not missense. Details ▾Hide ▴

Evidence considered

predicted protein consequence is p.(Arg369=)

BP3 N/AThis criterion applies to in-frame deletions or insertions in repetitive regions without known function. This variant is a synonymous single-nucleotide substitution. Details ▾Hide ▴

Evidence considered

single-nucleotide synonymous substitution

Identifiers

Gene: WT1
Transcript: NM_024426.4
Coding (HGVS c.): NM_024426.4:c.1107A>G
Protein (HGVS p.): NP_077744.3:p.(Arg369=)
GRCh38: chr11:32396399 T>C
GRCh37: chr11:32417945 T>C

Gene diagram

Every interpreted variant in WT1, mapped onto the exon structure of NM_024426.4. Select a row to find it on the plot.

WT1NM_024426.4

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 WT1 — Select a row to find it on the plot; use the link to open its page.

	Protein	Location	Classification	Link

gnomAD v4.1 291,078 / 1,613,638 alleles AF 0.18 · 35597 homozygotes · FAF 0.665

gnomAD v2.1 66,569 / 282,422 alleles AF 0.236 · 11532 homozygotes · FAF 0.686

By genetic ancestry

gnomAD v4.1

AF 0.18 · 291078 / 1,613,638 alleles · 35597 hom · FAF 0.66

East Asian30108 / 44,860	0.6710092 hom
South Asian32191 / 91,058	0.355879 hom
Admixed American20521 / 59,984	0.343749 hom
Remaining individuals12655 / 62,492	0.21606 hom
Amish179 / 910	0.223 hom
Middle Eastern1124 / 5,992	0.19117 hom
Ashkenazi Jewish5273 / 29,608	0.18452 hom
European (Finnish)10979 / 63,800	0.17959 hom
European (non-Finnish)169781 / 1,179,968	0.1412283 hom
African/African American8267 / 74,966	0.11437 hom

gnomAD v2.1

AF 0.24 · 66569 / 282,422 alleles · 11532 hom · FAF 0.69

East Asian13903 / 19,922	0.74884 hom
Admixed American13014 / 35,402	0.372537 hom
South Asian10896 / 30,608	0.361975 hom
Remaining individuals1419 / 7,212	0.2140 hom
Ashkenazi Jewish1832 / 10,368	0.18156 hom
European (Finnish)4363 / 24,938	0.17363 hom
European (non-Finnish)18363 / 129,014	0.141329 hom
African/African American2779 / 24,958	0.11148 hom

Statements

gnomAD 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.

gnomAD v2.1

Other predictors

REVEL: Not available
BayesDel: Not available

How the predictions were used

Evidence considered

synonymous protein prediction p.(Arg369=)
SpliceAI max delta score 0.01

Sources

spliceai ↗

Evidence considered

synonymous protein prediction p.(Arg369=)
SpliceAI max delta score 0.01

Sources

spliceai ↗

Evidence considered

SpliceAI max delta score 0.01

Sources

spliceai ↗

Statement

In silico

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

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 v4.1 291,078 / 1,613,638 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 ↗

All source links

Statements for reports

The evidence statements recorded by the interpretation pipeline. They have not been reinterpreted by the page.

gnomAD v4.1

gnomAD v2.1

ClinVar

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

In silico

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

Functional

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

Somatic

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

Cancer Hotspots

This variant does not lie in a statistically significant hotspot.