NM_030761.5:c.313+2785A>G

Variant names:

• chr1-22126831-T-C
• rs10917157
• NM_030761.5:c.313+2785A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_030761.5(WNT4):​c.313+2785A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.05 in 152,314 control chromosomes in the GnomAD database, including 299 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.050 (299 hom., cov: 33)
• Consequence: WNT4 NM_030761.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.76
• Publications: 9 publications found

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]

WNT4 Gene-Disease associations (from GenCC):

• mullerian aplasia and hyperandrogenism

  Inheritance: AD Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Orphanet, Ambry Genetics
• SERKAL syndrome

  Inheritance: AR, Unknown Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Ambry Genetics, G2P, Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.193 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WNT4	NM_030761.5	c.313+2785A>G		intron_variant	Intron 2 of 4	ENST00000290167.11	NP_110388.2
WNT4	XM_011541597.3	c.379+2785A>G		intron_variant	Intron 2 of 4		XP_011539899.1
WNT4	XM_011541599.2	c.*436A>G		downstream_gene_variant			XP_011539901.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WNT4	ENST00000290167.11	c.313+2785A>G		intron_variant	Intron 2 of 4	1	NM_030761.5	ENSP00000290167.5
WNT4	ENST00000415567.1	c.*436A>G		downstream_gene_variant		2		ENSP00000403334.1

Frequencies

GnomAD3 genomes AF: 0.0500 AC: 7615 AN: 152196 Hom.: 298 Cov.: 33

Gnomad AFR AF: 0.0147

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.0680

Gnomad ASJ AF: 0.0559

Gnomad EAS AF: 0.203

Gnomad SAS AF: 0.0919

Gnomad FIN AF: 0.0384

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0546

Gnomad OTH AF: 0.0602

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0500 AC: 7622 AN: 152314 Hom.: 299 Cov.: 33 AF XY: 0.0519 AC XY: 3863 AN XY: 74478

African (AFR) AF: 0.0148 AC: 614 AN: 41574

American (AMR) AF: 0.0682 AC: 1044 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0559 AC: 194 AN: 3472

East Asian (EAS) AF: 0.203 AC: 1048 AN: 5168

South Asian (SAS) AF: 0.0926 AC: 447 AN: 4828

European-Finnish (FIN) AF: 0.0384 AC: 408 AN: 10622

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.0546 AC: 3713 AN: 68022

Other (OTH) AF: 0.0595 AC: 126 AN: 2116

Alfa AF: 0.0543 Hom.: 51

Bravo AF: 0.0520

Asia WGS AF: 0.143 AC: 497 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.55
DANN	Benign	0.38
PhyloP100		-1.8
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10917157; hg19: chr1-22453324;