1-22141722-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_030761.5(WNT4):c.77+1124G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.141 in 152,170 control chromosomes in the GnomAD database, including 2,295 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 0.14 (2295 hom., cov: 32)
• Consequence: WNT4 NM_030761.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.37

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]

LOC105376845 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.25).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.489 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WNT4	NM_030761.5	c.77+1124G>A		intron_variant		ENST00000290167.11
LOC105376845	XR_947050.1	n.53+717C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WNT4	ENST00000290167.11	c.77+1124G>A		intron_variant		1	NM_030761.5	P1
WNT4	ENST00000441048.1	c.-89+2010G>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.141 AC: 21402 AN: 152052 Hom.: 2293 Cov.: 32

Gnomad AFR AF: 0.0334

Gnomad AMI AF: 0.280

Gnomad AMR AF: 0.248

Gnomad ASJ AF: 0.0773

Gnomad EAS AF: 0.505

Gnomad SAS AF: 0.206

Gnomad FIN AF: 0.150

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.150

Gnomad OTH AF: 0.132

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

GnomAD4 genome AF: 0.141 AC: 21412 AN: 152170 Hom.: 2295 Cov.: 32 AF XY: 0.148 AC XY: 10984 AN XY: 74390

Gnomad4 AFR AF: 0.0333

Gnomad4 AMR AF: 0.248

Gnomad4 ASJ AF: 0.0773

Gnomad4 EAS AF: 0.505

Gnomad4 SAS AF: 0.207

Gnomad4 FIN AF: 0.150

Gnomad4 NFE AF: 0.150

Gnomad4 OTH AF: 0.132

Alfa AF: 0.129 Hom.: 259

Bravo AF: 0.146

Asia WGS AF: 0.298 AC: 1035 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.25
Cadd	Uncertain	23
Dann	Benign	0.85

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

Other links and lift over

dbSNP: rs3820282; hg19: chr1-22468215;