chr17-46790821-G-A

Position:

• chr17-46790821-G-A

Variant summary

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

The NM_030753.5(WNT3):​c.81-16912C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.513 in 152,088 control chromosomes in the GnomAD database, including 20,502 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 0.51 (20502 hom., cov: 33)
• Consequence: WNT3 NM_030753.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.688

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=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.639 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WNT3	NM_030753.5	c.81-16912C>T		intron_variant		ENST00000225512.6
LRRC37A2	XM_024450773.2	c.4809+240302G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WNT3	ENST00000225512.6	c.81-16912C>T		intron_variant		1	NM_030753.5	P1
WNT3	ENST00000706495.1	c.-115-16912C>T		intron_variant
WNT3	ENST00000573788.5	n.492-16912C>T		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.513 AC: 78012 AN: 151970 Hom.: 20472 Cov.: 33

Gnomad AFR AF: 0.591

Gnomad AMI AF: 0.431

Gnomad AMR AF: 0.566

Gnomad ASJ AF: 0.512

Gnomad EAS AF: 0.630

Gnomad SAS AF: 0.659

Gnomad FIN AF: 0.474

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.444

Gnomad OTH AF: 0.481

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

GnomAD4 genome AF: 0.513 AC: 78094 AN: 152088 Hom.: 20502 Cov.: 33 AF XY: 0.519 AC XY: 38566 AN XY: 74346

Gnomad4 AFR AF: 0.591

Gnomad4 AMR AF: 0.566

Gnomad4 ASJ AF: 0.512

Gnomad4 EAS AF: 0.629

Gnomad4 SAS AF: 0.658

Gnomad4 FIN AF: 0.474

Gnomad4 NFE AF: 0.444

Gnomad4 OTH AF: 0.483

Alfa AF: 0.469 Hom.: 17630

Bravo AF: 0.522

Asia WGS AF: 0.683 AC: 2371 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.55
DANN	Benign	0.70

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: rs12452064; hg19: chr17-44868187;