1-22120823-A-G

Position:

• chr1-22120823-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_030761.5(WNT4):​c.589-306T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.232 in 152,026 control chromosomes in the GnomAD database, including 4,960 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.23 (4960 hom., cov: 32)
• Consequence: WNT4 NM_030761.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.368

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 1-22120823-A-G is Benign according to our data. Variant chr1-22120823-A-G is described in ClinVar as [Benign]. Clinvar id is 1263499.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.672 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WNT4	NM_030761.5	c.589-306T>C		intron_variant		ENST00000290167.11	NP_110388.2
WNT4	XM_011541597.3	c.655-306T>C		intron_variant			XP_011539899.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WNT4	ENST00000290167.11	c.589-306T>C		intron_variant		1	NM_030761.5	ENSP00000290167	P1

Frequencies

GnomAD3 genomes AF: 0.232 AC: 35285 AN: 151908 Hom.: 4952 Cov.: 32

Gnomad AFR AF: 0.173

Gnomad AMI AF: 0.294

Gnomad AMR AF: 0.338

Gnomad ASJ AF: 0.143

Gnomad EAS AF: 0.691

Gnomad SAS AF: 0.346

Gnomad FIN AF: 0.205

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.211

Gnomad OTH AF: 0.223

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

GnomAD4 genome AF: 0.232 AC: 35312 AN: 152026 Hom.: 4960 Cov.: 32 AF XY: 0.241 AC XY: 17907 AN XY: 74316

Gnomad4 AFR AF: 0.173

Gnomad4 AMR AF: 0.339

Gnomad4 ASJ AF: 0.143

Gnomad4 EAS AF: 0.691

Gnomad4 SAS AF: 0.347

Gnomad4 FIN AF: 0.205

Gnomad4 NFE AF: 0.211

Gnomad4 OTH AF: 0.222

Alfa AF: 0.224 Hom.: 2126

Bravo AF: 0.243

Asia WGS AF: 0.467 AC: 1619 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 13, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.67
DANN	Benign	0.26

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: rs3765350; hg19: chr1-22447316;