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1-22120197-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2

The NM_030761.5(WNT4):c.909C>T(p.Ile303=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000453 in 1,613,870 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0021 ( 2 hom., cov: 33)
Exomes 𝑓: 0.00028 ( 0 hom. )

Consequence

WNT4
NM_030761.5 synonymous

Scores

2

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.170
Variant links:
Genes affected
WNT4 (HGNC:12783): (Wnt family member 4) The WNT gene family consists of structurally related genes which encode secreted signaling proteins. These proteins have been implicated in oncogenesis and in several developmental processes, including regulation of cell fate and patterning during embryogenesis. This gene is a member of the WNT gene family, and is the first signaling molecule shown to influence the sex-determination cascade. It encodes a protein which shows 98% amino acid identity to the Wnt4 protein of mouse and rat. This gene and a nuclear receptor known to antagonize the testis-determining factor play a concerted role in both the control of female development and the prevention of testes formation. This gene and another two family members, WNT2 and WNT7B, may be associated with abnormal proliferation in breast tissue. Mutations in this gene can result in Rokitansky-Kuster-Hauser syndrome and in SERKAL syndrome. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.34).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 1-22120197-G-A is Benign according to our data. Variant chr1-22120197-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 772452.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-0.17 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 2 AD,AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
WNT4NM_030761.5 linkuse as main transcriptc.909C>T p.Ile303= synonymous_variant 5/5 ENST00000290167.11
WNT4XM_011541597.3 linkuse as main transcriptc.975C>T p.Ile325= synonymous_variant 5/5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
WNT4ENST00000290167.11 linkuse as main transcriptc.909C>T p.Ile303= synonymous_variant 5/51 NM_030761.5 P1P56705-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00212
AC:
323
AN:
152278
Hom.:
2
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00719
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000785
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00115
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000441
Gnomad OTH
AF:
0.00143
GnomAD3 exomes
AF:
0.000825
AC:
207
AN:
250846
Hom.:
1
AF XY:
0.000641
AC XY:
87
AN XY:
135726
show subpopulations
Gnomad AFR exome
AF:
0.00772
Gnomad AMR exome
AF:
0.000723
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00212
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.000139
Gnomad NFE exome
AF:
0.0000882
Gnomad OTH exome
AF:
0.000653
GnomAD4 exome
AF:
0.000278
AC:
406
AN:
1461474
Hom.:
0
Cov.:
31
AF XY:
0.000217
AC XY:
158
AN XY:
727064
show subpopulations
Gnomad4 AFR exome
AF:
0.00723
Gnomad4 AMR exome
AF:
0.000649
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000378
Gnomad4 SAS exome
AF:
0.0000580
Gnomad4 FIN exome
AF:
0.000169
Gnomad4 NFE exome
AF:
0.0000495
Gnomad4 OTH exome
AF:
0.000811
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00213
AC:
325
AN:
152396
Hom.:
2
Cov.:
33
AF XY:
0.00209
AC XY:
156
AN XY:
74526
show subpopulations
Gnomad4 AFR
AF:
0.00721
Gnomad4 AMR
AF:
0.000784
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00116
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000441
Gnomad4 OTH
AF:
0.00142
Alfa
AF:
0.00140
Hom.:
0
Bravo
AF:
0.00281
Asia WGS
AF:
0.000866
AC:
3
AN:
3478
EpiCase
AF:
0.0000545
EpiControl
AF:
0.0000593

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeNov 15, 2023- -
Mullerian aplasia and hyperandrogenism;C2678492:SERKAL syndrome Benign:1
Likely benign, criteria provided, single submitterclinical testingFulgent Genetics, Fulgent GeneticsJul 29, 2021- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.34
Cadd
Benign
5.2
Dann
Benign
0.94

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs112452625; hg19: chr1-22446690; COSMIC: COSV51603088; API