12-1623129-G-C

Variant names:

• chr12-1623129-G-C
• rs6489301
• ENST00000310594.7:c.-58+5986G>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.592 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000310594.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WNT5B	NM_030775.2		c.-58+5986G>C		intron	N/A	NP_110402.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WNT5B	ENST00000310594.7	TSL:1	c.-58+5986G>C		intron	N/A	ENSP00000308887.3
	WNT5B	ENST00000537031.5	TSL:2	c.-57-8169G>C		intron	N/A	ENSP00000439312.1
	WNT5B	ENST00000545811.5	TSL:2	c.-57-8169G>C		intron	N/A	ENSP00000445395.1

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

African (AFR) AF: 0.599 AC: 24169 AN: 40374

American (AMR) AF: 0.406 AC: 6091 AN: 15010

Ashkenazi Jewish (ASJ) AF: 0.501 AC: 1732 AN: 3460

East Asian (EAS) AF: 0.257 AC: 1319 AN: 5126

South Asian (SAS) AF: 0.490 AC: 2323 AN: 4744

European-Finnish (FIN) AF: 0.619 AC: 6197 AN: 10010

Middle Eastern (MID) AF: 0.497 AC: 145 AN: 292

European-Non Finnish (NFE) AF: 0.540 AC: 36480 AN: 67610

Other (OTH) AF: 0.519 AC: 1080 AN: 2080

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.3
DANN	Benign	0.57
PhyloP100		1.4
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: rs6489301; hg19: chr12-1732295;