12-1612088-T-G

Variant names:

• chr12-1612088-T-G
• rs4765830
• ENST00000537031.5:c.-57-19210T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000537031.5(WNT5B):​c.-57-19210T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.676 in 152,002 control chromosomes in the GnomAD database, including 35,714 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 0.68 (35714 hom., cov: 32)
• Consequence: WNT5B ENST00000537031.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.68
• Publications: 4 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.756 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WNT5B	ENST00000537031.5	c.-57-19210T>G		intron_variant	Intron 1 of 4	2		ENSP00000439312.1
WNT5B	ENST00000545811.5	c.-57-19210T>G		intron_variant	Intron 1 of 3	2		ENSP00000445395.1
WNT5B	ENST00000539198.5	c.-57-19210T>G		intron_variant	Intron 1 of 3	4		ENSP00000438414.1

Frequencies

GnomAD3 genomes AF: 0.677 AC: 102762 AN: 151884 Hom.: 35696 Cov.: 32

Gnomad AFR AF: 0.556

Gnomad AMI AF: 0.620

Gnomad AMR AF: 0.594

Gnomad ASJ AF: 0.778

Gnomad EAS AF: 0.435

Gnomad SAS AF: 0.719

Gnomad FIN AF: 0.785

Gnomad MID AF: 0.785

Gnomad NFE AF: 0.761

Gnomad OTH AF: 0.702

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

GnomAD4 genome AF: 0.676 AC: 102817 AN: 152002 Hom.: 35714 Cov.: 32 AF XY: 0.676 AC XY: 50247 AN XY: 74300

African (AFR) AF: 0.556 AC: 23014 AN: 41418

American (AMR) AF: 0.593 AC: 9057 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.778 AC: 2698 AN: 3468

East Asian (EAS) AF: 0.435 AC: 2246 AN: 5166

South Asian (SAS) AF: 0.719 AC: 3462 AN: 4812

European-Finnish (FIN) AF: 0.785 AC: 8283 AN: 10554

Middle Eastern (MID) AF: 0.779 AC: 229 AN: 294

European-Non Finnish (NFE) AF: 0.761 AC: 51773 AN: 67996

Other (OTH) AF: 0.705 AC: 1491 AN: 2114

Alfa AF: 0.630 Hom.: 2985

Bravo AF: 0.652

Asia WGS AF: 0.577 AC: 2009 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.015
DANN	Benign	0.52
PhyloP100		-1.7
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4765830; hg19: chr12-1721254;