chr17-46770948-G-T

Variant names:

• chr17-46770948-G-T
• rs3809857
• NM_030753.5:c.323-900C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_030753.5(WNT3):​c.323-900C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.248 in 152,258 control chromosomes in the GnomAD database, including 5,872 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 0.25 (5872 hom., cov: 33)
• Consequence: WNT3 NM_030753.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.356
• Publications: 25 publications found

Genes affected

WNT3 (HGNC:12782): (Wnt family member 3) 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 98% amino acid identity to mouse Wnt3 protein, and 84% to human WNT3A protein, another WNT gene product. The mouse studies show the requirement of Wnt3 in primary axis formation in the mouse. Studies of the gene expression suggest that this gene may play a key role in some cases of human breast, rectal, lung, and gastric cancer through activation of the WNT-beta-catenin-TCF signaling pathway. This gene is clustered with WNT15, another family member, in the chromosome 17q21 region. [provided by RefSeq, Jul 2008]

LRRC37A2 (HGNC:32404): (leucine rich repeat containing 37 member A2) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.323 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WNT3	NM_030753.5	c.323-900C>A		intron_variant	Intron 2 of 4	ENST00000225512.6	NP_110380.1
LRRC37A2	XM_024450773.2	c.4809+220429G>T		intron_variant	Intron 10 of 10		XP_024306541.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WNT3	ENST00000225512.6	c.323-900C>A		intron_variant	Intron 2 of 4	1	NM_030753.5	ENSP00000225512.5

Frequencies

GnomAD3 genomes AF: 0.248 AC: 37721 AN: 152140 Hom.: 5864 Cov.: 33

Gnomad AFR AF: 0.0580

Gnomad AMI AF: 0.415

Gnomad AMR AF: 0.254

Gnomad ASJ AF: 0.217

Gnomad EAS AF: 0.295

Gnomad SAS AF: 0.235

Gnomad FIN AF: 0.459

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.326

Gnomad OTH AF: 0.239

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

GnomAD4 genome AF: 0.248 AC: 37736 AN: 152258 Hom.: 5872 Cov.: 33 AF XY: 0.256 AC XY: 19032 AN XY: 74456

African (AFR) AF: 0.0579 AC: 2406 AN: 41586

American (AMR) AF: 0.254 AC: 3889 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.217 AC: 754 AN: 3468

East Asian (EAS) AF: 0.295 AC: 1529 AN: 5176

South Asian (SAS) AF: 0.236 AC: 1139 AN: 4826

European-Finnish (FIN) AF: 0.459 AC: 4869 AN: 10606

Middle Eastern (MID) AF: 0.286 AC: 84 AN: 294

European-Non Finnish (NFE) AF: 0.326 AC: 22171 AN: 67974

Other (OTH) AF: 0.245 AC: 518 AN: 2114

Alfa AF: 0.310 Hom.: 4058

Bravo AF: 0.222

Asia WGS AF: 0.237 AC: 822 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	7.0
DANN	Benign	0.83
PhyloP100		0.36
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs3809857; hg19: chr17-44848314;