17-46779275-G-C

Position:

• chr17-46779275-G-C

Variant summary

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

The NM_030753.5(WNT3):​c.81-5366C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.841 in 152,234 control chromosomes in the GnomAD database, including 54,091 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 0.84 (54091 hom., cov: 33)
• Consequence: WNT3 NM_030753.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.646

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=-0.55).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WNT3	NM_030753.5	c.81-5366C>G		intron_variant		ENST00000225512.6	NP_110380.1
LRRC37A2	XM_024450773.2	c.4809+228756G>C		intron_variant			XP_024306541.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WNT3	ENST00000225512.6	c.81-5366C>G		intron_variant		1	NM_030753.5	ENSP00000225512	P1
WNT3	ENST00000706495.1	c.-115-5366C>G		intron_variant				ENSP00000516418
WNT3	ENST00000573788.5	n.492-5366C>G		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.840 AC: 127833 AN: 152116 Hom.: 54030 Cov.: 33

Gnomad AFR AF: 0.880

Gnomad AMI AF: 0.739

Gnomad AMR AF: 0.822

Gnomad ASJ AF: 0.743

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.940

Gnomad FIN AF: 0.927

Gnomad MID AF: 0.778

Gnomad NFE AF: 0.795

Gnomad OTH AF: 0.812

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

GnomAD4 genome AF: 0.841 AC: 127956 AN: 152234 Hom.: 54091 Cov.: 33 AF XY: 0.849 AC XY: 63223 AN XY: 74430

Gnomad4 AFR AF: 0.880

Gnomad4 AMR AF: 0.822

Gnomad4 ASJ AF: 0.743

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.941

Gnomad4 FIN AF: 0.927

Gnomad4 NFE AF: 0.795

Gnomad4 OTH AF: 0.815

Alfa AF: 0.829 Hom.: 6528

Bravo AF: 0.832

Asia WGS AF: 0.968 AC: 3366 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	11
DANN	Benign	0.72

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: rs199515; hg19: chr17-44856641;