12-1631005-C-G

Position:

• chr12-1631005-C-G

Variant summary

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

The ENST00000543071(WNT5B):​c.-350C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0659 in 180,624 control chromosomes in the GnomAD database, including 734 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 0.069 (634 hom., cov: 32)
  • Exomes 𝑓: 0.047 (100 hom.)
• Consequence: WNT5B ENST00000543071 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.12

Genes affected

WNT5B (HGNC:16265): (Wnt family member 5B) 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 94% and 80% amino acid identity to the mouse Wnt5b protein and the human WNT5A protein, respectively. Alternative splicing of this gene generates 2 transcript variants. [provided by RefSeq, Jul 2008]

WNT5B (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.217 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WNT5B	NM_032642.3	c.-57-293C>G		intron_variant		ENST00000397196.7	NP_116031.1
WNT5B	NM_030775.2	c.-57-293C>G		intron_variant			NP_110402.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WNT5B	ENST00000397196.7	c.-57-293C>G		intron_variant		1	NM_032642.3	ENSP00000380379.2

Frequencies

GnomAD3 genomes AF: 0.0693 AC: 10536 AN: 152064 Hom.: 632 Cov.: 32

Gnomad AFR AF: 0.148

Gnomad AMI AF: 0.00330

Gnomad AMR AF: 0.0624

Gnomad ASJ AF: 0.0150

Gnomad EAS AF: 0.228

Gnomad SAS AF: 0.0699

Gnomad FIN AF: 0.0363

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0203

Gnomad OTH AF: 0.0574

GnomAD4 exome AF: 0.0469 AC: 1334 AN: 28442 Hom.: 100 Cov.: 0 AF XY: 0.0436 AC XY: 637 AN XY: 14608

Gnomad4 AFR exome AF: 0.124

Gnomad4 AMR exome AF: 0.0523

Gnomad4 ASJ exome AF: 0.0152

Gnomad4 EAS exome AF: 0.264

Gnomad4 SAS exome AF: 0.0630

Gnomad4 FIN exome AF: 0.0235

Gnomad4 NFE exome AF: 0.0174

Gnomad4 OTH exome AF: 0.0367

GnomAD4 genome AF: 0.0694 AC: 10561 AN: 152182 Hom.: 634 Cov.: 32 AF XY: 0.0706 AC XY: 5257 AN XY: 74410

Gnomad4 AFR AF: 0.148

Gnomad4 AMR AF: 0.0624

Gnomad4 ASJ AF: 0.0150

Gnomad4 EAS AF: 0.228

Gnomad4 SAS AF: 0.0692

Gnomad4 FIN AF: 0.0363

Gnomad4 NFE AF: 0.0203

Gnomad4 OTH AF: 0.0616

Alfa AF: 0.0470 Hom.: 46

Bravo AF: 0.0743

Asia WGS AF: 0.165 AC: 574 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.22
DANN	Benign	0.31

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: rs10773971; hg19: chr12-1740171;