rs199520

Variant names:

• chr17-46776506-G-A
• rs199520
• NM_030753.5:c.81-2597C>T

Your query was ambiguous. Multiple possible variants found:

• chr17-46776506-G-A
• chr17-46776506-G-T

Variant summary

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

The NM_030753.5(WNT3):​c.81-2597C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.625 in 152,092 control chromosomes in the GnomAD database, including 32,347 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 0.62 (32347 hom., cov: 32)
• Consequence: WNT3 NM_030753.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.589
• Publications: 32 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=-0.71).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.796 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WNT3	NM_030753.5	c.81-2597C>T		intron_variant	Intron 1 of 4	ENST00000225512.6	NP_110380.1
LRRC37A2	XM_024450773.2	c.4809+225987G>A		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.81-2597C>T		intron_variant	Intron 1 of 4	1	NM_030753.5	ENSP00000225512.5
WNT3	ENST00000706495.1	c.-115-2597C>T		intron_variant	Intron 2 of 5			ENSP00000516418.1
WNT3	ENST00000573788.5	n.492-2597C>T		intron_variant	Intron 3 of 3	4

Frequencies

GnomAD3 genomes AF: 0.625 AC: 95027 AN: 151974 Hom.: 32346 Cov.: 32

Gnomad AFR AF: 0.364

Gnomad AMI AF: 0.666

Gnomad AMR AF: 0.564

Gnomad ASJ AF: 0.679

Gnomad EAS AF: 0.395

Gnomad SAS AF: 0.817

Gnomad FIN AF: 0.856

Gnomad MID AF: 0.630

Gnomad NFE AF: 0.762

Gnomad OTH AF: 0.634

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

GnomAD4 genome AF: 0.625 AC: 95054 AN: 152092 Hom.: 32347 Cov.: 32 AF XY: 0.631 AC XY: 46944 AN XY: 74380

African (AFR) AF: 0.364 AC: 15086 AN: 41454

American (AMR) AF: 0.563 AC: 8609 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.679 AC: 2359 AN: 3472

East Asian (EAS) AF: 0.395 AC: 2046 AN: 5174

South Asian (SAS) AF: 0.818 AC: 3946 AN: 4826

European-Finnish (FIN) AF: 0.856 AC: 9073 AN: 10600

Middle Eastern (MID) AF: 0.633 AC: 186 AN: 294

European-Non Finnish (NFE) AF: 0.762 AC: 51800 AN: 67972

Other (OTH) AF: 0.636 AC: 1342 AN: 2110

Alfa AF: 0.725 Hom.: 16312

Bravo AF: 0.581

Asia WGS AF: 0.605 AC: 2103 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	7.4
DANN	Benign	0.85
PhyloP100		-0.59
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: rs199520; hg19: chr17-44853872;