17-46800902-T-C

Variant names:

• chr17-46800902-T-C
• rs10514911
• NM_030753.5:c.80+17616A>G

Variant summary

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

The NM_030753.5(WNT3):​c.80+17616A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.843 in 152,146 control chromosomes in the GnomAD database, including 54,539 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 (54539 hom., cov: 31)
• Consequence: WNT3 NM_030753.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.84

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:32404): (leucine rich repeat containing 37 member A2) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

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 (EAS) allele frequency at 95% confidence interval = 0.917 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WNT3	NM_030753.5	c.80+17616A>G		intron_variant	Intron 1 of 4	ENST00000225512.6	NP_110380.1
LRRC37A2	XM_024450773.2	c.4810-248154T>C		intron_variant	Intron 10 of 10		XP_024306541.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WNT3	ENST00000225512.6	c.80+17616A>G		intron_variant	Intron 1 of 4	1	NM_030753.5	ENSP00000225512.5
WNT3	ENST00000706495.1	c.-115-26993A>G		intron_variant	Intron 2 of 5			ENSP00000516418.1
WNT3	ENST00000573788.5	n.491+20206A>G		intron_variant	Intron 3 of 3	4

Frequencies

GnomAD3 genomes AF: 0.843 AC: 128147 AN: 152028 Hom.: 54502 Cov.: 31

Gnomad AFR AF: 0.720

Gnomad AMI AF: 0.877

Gnomad AMR AF: 0.855

Gnomad ASJ AF: 0.910

Gnomad EAS AF: 0.939

Gnomad SAS AF: 0.921

Gnomad FIN AF: 0.876

Gnomad MID AF: 0.896

Gnomad NFE AF: 0.892

Gnomad OTH AF: 0.858

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

GnomAD4 genome AF: 0.843 AC: 128245 AN: 152146 Hom.: 54539 Cov.: 31 AF XY: 0.843 AC XY: 62747 AN XY: 74408

Gnomad4 AFR AF: 0.720

Gnomad4 AMR AF: 0.856

Gnomad4 ASJ AF: 0.910

Gnomad4 EAS AF: 0.939

Gnomad4 SAS AF: 0.921

Gnomad4 FIN AF: 0.876

Gnomad4 NFE AF: 0.892

Gnomad4 OTH AF: 0.860

Alfa AF: 0.884 Hom.: 61123

Bravo AF: 0.837

Asia WGS AF: 0.930 AC: 3236 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	0.045
DANN	Benign	0.32

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: rs10514911; hg19: chr17-44878268;