rs9890413

Positions:

• chr17-46824083-G-A
• chr17-46824083-G-C
• chr17-46824083-G-T

Variant summary

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

The ENST00000706495.1(WNT3):​c.-116+7365C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.637 in 151,804 control chromosomes in the GnomAD database, including 31,752 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 0.64 (31752 hom., cov: 30)
• Consequence: WNT3 ENST00000706495.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.268

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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.916 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRRC37A2	XM_024450773.2	c.4810-224973G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WNT3	ENST00000706495.1	c.-116+7365C>T		intron_variant
WNT3	ENST00000573788.5	n.386-2870C>T		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.637 AC: 96633 AN: 151686 Hom.: 31755 Cov.: 30

Gnomad AFR AF: 0.492

Gnomad AMI AF: 0.613

Gnomad AMR AF: 0.731

Gnomad ASJ AF: 0.725

Gnomad EAS AF: 0.938

Gnomad SAS AF: 0.850

Gnomad FIN AF: 0.614

Gnomad MID AF: 0.712

Gnomad NFE AF: 0.664

Gnomad OTH AF: 0.660

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

GnomAD4 genome AF: 0.637 AC: 96673 AN: 151804 Hom.: 31752 Cov.: 30 AF XY: 0.641 AC XY: 47549 AN XY: 74192

Gnomad4 AFR AF: 0.492

Gnomad4 AMR AF: 0.731

Gnomad4 ASJ AF: 0.725

Gnomad4 EAS AF: 0.938

Gnomad4 SAS AF: 0.849

Gnomad4 FIN AF: 0.614

Gnomad4 NFE AF: 0.664

Gnomad4 OTH AF: 0.661

Alfa AF: 0.653 Hom.: 9930

Bravo AF: 0.639

Asia WGS AF: 0.880 AC: 3057 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.1
DANN	Benign	0.49

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs9890413; hg19: chr17-44901449;