rs2235529

Positions:

• chr1-22123994-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_030761.5(WNT4):​c.314-2418G>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 152,286 control chromosomes in the GnomAD database, including 2,302 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 (2302 hom., cov: 32)
• Consequence: WNT4 NM_030761.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.263

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.484 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WNT4	NM_030761.5	c.314-2418G>A		intron_variant		ENST00000290167.11	NP_110388.2
WNT4	XM_011541597.3	c.380-2418G>A		intron_variant			XP_011539899.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WNT4	ENST00000290167.11	c.314-2418G>A		intron_variant		1	NM_030761.5	ENSP00000290167	P1

Frequencies

GnomAD3 genomes AF: 0.141 AC: 21432 AN: 152168 Hom.: 2300 Cov.: 32

Gnomad AFR AF: 0.0328

Gnomad AMI AF: 0.280

Gnomad AMR AF: 0.244

Gnomad ASJ AF: 0.0766

Gnomad EAS AF: 0.501

Gnomad SAS AF: 0.222

Gnomad FIN AF: 0.157

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.150

Gnomad OTH AF: 0.135

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

GnomAD4 genome AF: 0.141 AC: 21441 AN: 152286 Hom.: 2302 Cov.: 32 AF XY: 0.148 AC XY: 11018 AN XY: 74462

Gnomad4 AFR AF: 0.0327

Gnomad4 AMR AF: 0.245

Gnomad4 ASJ AF: 0.0766

Gnomad4 EAS AF: 0.500

Gnomad4 SAS AF: 0.223

Gnomad4 FIN AF: 0.157

Gnomad4 NFE AF: 0.150

Gnomad4 OTH AF: 0.134

Alfa AF: 0.152 Hom.: 3558

Bravo AF: 0.146

Asia WGS AF: 0.306 AC: 1061 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	7.4
DANN	Benign	0.75

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2235529; hg19: chr1-22450487;