17-46768172-C-T

Position:

• chr17-46768172-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_030753.5(WNT3):​c.*8+140G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0169 in 1,246,776 control chromosomes in the GnomAD database, including 258 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.014 (20 hom., cov: 32)
  • Exomes 𝑓: 0.017 (238 hom.)
• Consequence: WNT3 NM_030753.5 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.606

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BP6: Variant 17-46768172-C-T is Benign according to our data. Variant chr17-46768172-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1318109.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.014 (2140/152316) while in subpopulation NFE AF= 0.0214 (1457/68032). AF 95% confidence interval is 0.0205. There are 20 homozygotes in gnomad4. There are 1015 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 20 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WNT3	NM_030753.5	c.*8+140G>A		intron_variant		ENST00000225512.6	NP_110380.1
LRRC37A2	XM_024450773.2	c.4809+217653C>T		intron_variant			XP_024306541.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WNT3	ENST00000225512.6	c.*8+140G>A		intron_variant		1	NM_030753.5	ENSP00000225512.5

Frequencies

GnomAD3 genomes AF: 0.0141 AC: 2140 AN: 152198 Hom.: 20 Cov.: 32

Gnomad AFR AF: 0.00398

Gnomad AMI AF: 0.0581

Gnomad AMR AF: 0.00465

Gnomad ASJ AF: 0.00375

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00311

Gnomad FIN AF: 0.0333

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0214

Gnomad OTH AF: 0.00574

GnomAD4 exome AF: 0.0173 AC: 18967 AN: 1094460 Hom.: 238 AF XY: 0.0171 AC XY: 9352 AN XY: 547720

Gnomad4 AFR exome AF: 0.00274

Gnomad4 AMR exome AF: 0.00277

Gnomad4 ASJ exome AF: 0.00346

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00204

Gnomad4 FIN exome AF: 0.0365

Gnomad4 NFE exome AF: 0.0202

Gnomad4 OTH exome AF: 0.0138

GnomAD4 genome AF: 0.0140 AC: 2140 AN: 152316 Hom.: 20 Cov.: 32 AF XY: 0.0136 AC XY: 1015 AN XY: 74476

Gnomad4 AFR AF: 0.00397

Gnomad4 AMR AF: 0.00464

Gnomad4 ASJ AF: 0.00375

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00311

Gnomad4 FIN AF: 0.0333

Gnomad4 NFE AF: 0.0214

Gnomad4 OTH AF: 0.00568

Alfa AF: 0.0190 Hom.: 10

Bravo AF: 0.0115

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 16, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	14
DANN	Benign	0.82

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs77266163; hg19: chr17-44845538;