chr1-228009795-G-A

Variant names:

• chr1-228009795-G-A
• rs708114
• NM_033131.4:c.71+2596G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
WNT3A	NM_033131.4	c.71+2596G>A		intron_variant	Intron 1 of 3	ENST00000284523.2	NP_149122.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WNT3A	ENST00000284523.2	c.71+2596G>A		intron_variant	Intron 1 of 3	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

African (AFR) AF: 0.357 AC: 14809 AN: 41492

American (AMR) AF: 0.489 AC: 7482 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.542 AC: 1879 AN: 3466

East Asian (EAS) AF: 0.570 AC: 2943 AN: 5162

South Asian (SAS) AF: 0.592 AC: 2856 AN: 4824

European-Finnish (FIN) AF: 0.580 AC: 6145 AN: 10596

Middle Eastern (MID) AF: 0.622 AC: 183 AN: 294

European-Non Finnish (NFE) AF: 0.530 AC: 36023 AN: 67964

Other (OTH) AF: 0.508 AC: 1073 AN: 2112

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
PhyloP100		0.67
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs708114; hg19: chr1-228197496;