rs199496

Positions:

• chr17-46789361-G-A
• chr17-46789361-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.81-15452C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.105 in 152,202 control chromosomes in the GnomAD database, including 974 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 0.11 (974 hom., cov: 32)
• Consequence: WNT3 NM_030753.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.791

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.159 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WNT3	NM_030753.5	c.81-15452C>T		intron_variant		ENST00000225512.6
LRRC37A2	XM_024450773.2	c.4809+238842G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WNT3	ENST00000225512.6	c.81-15452C>T		intron_variant		1	NM_030753.5	P1
WNT3	ENST00000706495.1	c.-115-15452C>T		intron_variant
WNT3	ENST00000573788.5	n.492-15452C>T		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.105 AC: 15996 AN: 152084 Hom.: 972 Cov.: 32

Gnomad AFR AF: 0.162

Gnomad AMI AF: 0.103

Gnomad AMR AF: 0.0720

Gnomad ASJ AF: 0.0953

Gnomad EAS AF: 0.0235

Gnomad SAS AF: 0.0251

Gnomad FIN AF: 0.0884

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0931

Gnomad OTH AF: 0.112

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

GnomAD4 genome AF: 0.105 AC: 16016 AN: 152202 Hom.: 974 Cov.: 32 AF XY: 0.102 AC XY: 7625 AN XY: 74422

Gnomad4 AFR AF: 0.162

Gnomad4 AMR AF: 0.0718

Gnomad4 ASJ AF: 0.0953

Gnomad4 EAS AF: 0.0236

Gnomad4 SAS AF: 0.0249

Gnomad4 FIN AF: 0.0884

Gnomad4 NFE AF: 0.0930

Gnomad4 OTH AF: 0.113

Alfa AF: 0.0944 Hom.: 777

Bravo AF: 0.105

Asia WGS AF: 0.0380 AC: 132 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.75
DANN	Benign	0.38

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: rs199496; hg19: chr17-44866727;