rs11655598

chr17-46790728-C-G

Variant summary

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

The NM_030753.5(WNT3):c.81-16819G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.194 in 152,196 control chromosomes in the GnomAD database, including 3,578 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 0.19 (3578 hom., cov: 32)
• Consequence: WNT3 NM_030753.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.797

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 (EAS) allele frequency at 95% confidence interval = 0.322 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WNT3	NM_030753.5	c.81-16819G>C		intron_variant		ENST00000225512.6
LRRC37A2	XM_024450773.2	c.4809+240209C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WNT3	ENST00000225512.6	c.81-16819G>C		intron_variant		1	NM_030753.5	P1
WNT3	ENST00000706495.1	c.-115-16819G>C		intron_variant
WNT3	ENST00000573788.5	n.492-16819G>C		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.194 AC: 29467 AN: 152078 Hom.: 3571 Cov.: 32

Gnomad AFR AF: 0.0466

Gnomad AMI AF: 0.199

Gnomad AMR AF: 0.178

Gnomad ASJ AF: 0.225

Gnomad EAS AF: 0.334

Gnomad SAS AF: 0.236

Gnomad FIN AF: 0.308

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.254

Gnomad OTH AF: 0.203

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

GnomAD4 genome AF: 0.194 AC: 29480 AN: 152196 Hom.: 3578 Cov.: 32 AF XY: 0.197 AC XY: 14639 AN XY: 74404

Gnomad4 AFR AF: 0.0464

Gnomad4 AMR AF: 0.178

Gnomad4 ASJ AF: 0.225

Gnomad4 EAS AF: 0.335

Gnomad4 SAS AF: 0.238

Gnomad4 FIN AF: 0.308

Gnomad4 NFE AF: 0.254

Gnomad4 OTH AF: 0.203

Alfa AF: 0.219 Hom.: 535

Bravo AF: 0.182

Asia WGS AF: 0.233 AC: 810 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	0.51
Dann	Benign	0.44

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: rs11655598; hg19: chr17-44868094;