12-1623129-G-C

Position:

• chr12-1623129-G-C

Variant summary

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

The ENST00000310594.7(WNT5B):​c.-58+5986G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.534 in 149,610 control chromosomes in the GnomAD database, including 21,942 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 0.53 (21942 hom., cov: 25)
• Consequence: WNT5B ENST00000310594.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.38

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.592 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WNT5B	NM_030775.2	c.-58+5986G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WNT5B	ENST00000310594.7	c.-58+5986G>C		intron_variant		1		P1
WNT5B	ENST00000537031.5	c.-57-8169G>C		intron_variant		2		P1
WNT5B	ENST00000539198.5	c.-57-8169G>C		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.534 AC: 79852 AN: 149500 Hom.: 21930 Cov.: 25

Gnomad AFR AF: 0.599

Gnomad AMI AF: 0.399

Gnomad AMR AF: 0.406

Gnomad ASJ AF: 0.501

Gnomad EAS AF: 0.258

Gnomad SAS AF: 0.491

Gnomad FIN AF: 0.619

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.540

Gnomad OTH AF: 0.521

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

GnomAD4 genome AF: 0.534 AC: 79897 AN: 149610 Hom.: 21942 Cov.: 25 AF XY: 0.534 AC XY: 38948 AN XY: 72920

Gnomad4 AFR AF: 0.599

Gnomad4 AMR AF: 0.406

Gnomad4 ASJ AF: 0.501

Gnomad4 EAS AF: 0.257

Gnomad4 SAS AF: 0.490

Gnomad4 FIN AF: 0.619

Gnomad4 NFE AF: 0.540

Gnomad4 OTH AF: 0.519

Alfa AF: 0.414 Hom.: 1123

Bravo AF: 0.522

Asia WGS AF: 0.406 AC: 1411 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.3
DANN	Benign	0.57

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: rs6489301; hg19: chr12-1732295;