chr17-46794621-C-T

Position:

• chr17-46794621-C-T

Variant summary

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

The NM_030753.5(WNT3):​c.81-20712G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.34 in 151,988 control chromosomes in the GnomAD database, including 9,255 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 0.34 (9255 hom., cov: 30)
• Consequence: WNT3 NM_030753.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.191

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:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.413 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WNT3	NM_030753.5	c.81-20712G>A		intron_variant		ENST00000225512.6	NP_110380.1
LRRC37A2	XM_024450773.2	c.4809+244102C>T		intron_variant			XP_024306541.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WNT3	ENST00000225512.6	c.81-20712G>A		intron_variant		1	NM_030753.5	ENSP00000225512	P1
WNT3	ENST00000706495.1	c.-115-20712G>A		intron_variant				ENSP00000516418
WNT3	ENST00000573788.5	n.492-20712G>A		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.340 AC: 51605 AN: 151870 Hom.: 9250 Cov.: 30

Gnomad AFR AF: 0.211

Gnomad AMI AF: 0.399

Gnomad AMR AF: 0.307

Gnomad ASJ AF: 0.372

Gnomad EAS AF: 0.327

Gnomad SAS AF: 0.294

Gnomad FIN AF: 0.403

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.417

Gnomad OTH AF: 0.347

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

GnomAD4 genome AF: 0.340 AC: 51631 AN: 151988 Hom.: 9255 Cov.: 30 AF XY: 0.337 AC XY: 25065 AN XY: 74288

Gnomad4 AFR AF: 0.211

Gnomad4 AMR AF: 0.307

Gnomad4 ASJ AF: 0.372

Gnomad4 EAS AF: 0.328

Gnomad4 SAS AF: 0.295

Gnomad4 FIN AF: 0.403

Gnomad4 NFE AF: 0.417

Gnomad4 OTH AF: 0.346

Alfa AF: 0.405 Hom.: 14257

Bravo AF: 0.333

Asia WGS AF: 0.261 AC: 912 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.0
DANN	Benign	0.67

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: rs111769; hg19: chr17-44871987;