chr1-228009795-G-A

Position:

• chr1-228009795-G-A

Variant summary

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

The NM_033131.4(WNT3A):​c.71+2596G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.486 in 152,118 control chromosomes in the GnomAD database, including 18,499 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 0.49 (18499 hom., cov: 33)
• Consequence: WNT3A NM_033131.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.674

Genes affected

WNT3A (HGNC:15983): (Wnt family member 3A) 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. It encodes a protein which shows 96% amino acid identity to mouse Wnt3A protein, and 84% to human WNT3 protein, another WNT gene product. This gene is clustered with WNT14 gene, another family member, in chromosome 1q42 region. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.574 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WNT3A	NM_033131.4	c.71+2596G>A		intron_variant		ENST00000284523.2	NP_149122.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WNT3A	ENST00000284523.2	c.71+2596G>A		intron_variant		1	NM_033131.4	ENSP00000284523.1

Frequencies

GnomAD3 genomes AF: 0.486 AC: 73888 AN: 151998 Hom.: 18490 Cov.: 33

Gnomad AFR AF: 0.357

Gnomad AMI AF: 0.584

Gnomad AMR AF: 0.489

Gnomad ASJ AF: 0.542

Gnomad EAS AF: 0.569

Gnomad SAS AF: 0.592

Gnomad FIN AF: 0.580

Gnomad MID AF: 0.604

Gnomad NFE AF: 0.530

Gnomad OTH AF: 0.503

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

GnomAD4 genome AF: 0.486 AC: 73924 AN: 152118 Hom.: 18499 Cov.: 33 AF XY: 0.490 AC XY: 36454 AN XY: 74354

Gnomad4 AFR AF: 0.357

Gnomad4 AMR AF: 0.489

Gnomad4 ASJ AF: 0.542

Gnomad4 EAS AF: 0.570

Gnomad4 SAS AF: 0.592

Gnomad4 FIN AF: 0.580

Gnomad4 NFE AF: 0.530

Gnomad4 OTH AF: 0.508

Alfa AF: 0.499 Hom.: 2604

Bravo AF: 0.470

Asia WGS AF: 0.582 AC: 2026 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.2
DANN	Benign	0.27

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: rs708114; hg19: chr1-228197496;