chr1-22143914-C-T

Position:

• chr1-22143914-C-T

Variant summary

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

The ENST00000648968.1(ENSG00000285873):​n.55+1010C>T variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.136 in 152,258 control chromosomes in the GnomAD database, including 2,203 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 (2202 hom., cov: 32)
  • Exomes 𝑓: 0.21 (1 hom.)
• Consequence: ENST00000648968.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0380

Genes affected

(HGNC:):

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=-0.77).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.492 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC105376845	XR_947050.1	n.53+2909C>T		intron_variant, non_coding_transcript_variant
LOC105376845	XR_947051.3	n.142+923C>T		intron_variant, non_coding_transcript_variant
LOC105376845	XR_947056.2	n.142+923C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
	ENST00000648968.1	n.55+1010C>T		intron_variant, non_coding_transcript_variant
WNT4	ENST00000441048.1	c.-271G>A		5_prime_UTR_variant	1/3	5		ENSP00000388925

Frequencies

GnomAD3 genomes AF: 0.136 AC: 20729 AN: 152082 Hom.: 2200 Cov.: 32

Gnomad AFR AF: 0.0317

Gnomad AMI AF: 0.224

Gnomad AMR AF: 0.241

Gnomad ASJ AF: 0.0698

Gnomad EAS AF: 0.508

Gnomad SAS AF: 0.194

Gnomad FIN AF: 0.164

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.143

Gnomad OTH AF: 0.125

GnomAD4 exome AF: 0.207 AC: 12 AN: 58 Hom.: 1 Cov.: 0 AF XY: 0.217 AC XY: 10 AN XY: 46

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.188

Gnomad4 NFE exome AF: 0.267

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.136 AC: 20738 AN: 152200 Hom.: 2202 Cov.: 32 AF XY: 0.144 AC XY: 10687 AN XY: 74408

Gnomad4 AFR AF: 0.0316

Gnomad4 AMR AF: 0.242

Gnomad4 ASJ AF: 0.0698

Gnomad4 EAS AF: 0.508

Gnomad4 SAS AF: 0.195

Gnomad4 FIN AF: 0.164

Gnomad4 NFE AF: 0.143

Gnomad4 OTH AF: 0.125

Alfa AF: 0.144 Hom.: 431

Bravo AF: 0.141

Asia WGS AF: 0.297 AC: 1030 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	8.0
DANN	Benign	0.54

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs56318008; hg19: chr1-22470407;