12-1625104-C-G

Variant names:

• chr12-1625104-C-G
• rs4766398
• ENST00000310594.7:c.-57-6194C>G

Variant summary

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

The NM_030775.2(WNT5B):​c.-57-6194C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.527 in 151,700 control chromosomes in the GnomAD database, including 21,346 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 (21346 hom., cov: 30)
• Consequence: WNT5B NM_030775.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.638
• Publications: 8 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=-1.0).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.558 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030775.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WNT5B	NM_030775.2		c.-57-6194C>G		intron	N/A	NP_110402.2	Q9H1J7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WNT5B	ENST00000310594.7	TSL:1	c.-57-6194C>G		intron	N/A	ENSP00000308887.3	Q9H1J7
	WNT5B	ENST00000537031.5	TSL:2	c.-57-6194C>G		intron	N/A	ENSP00000439312.1	Q9H1J7
	WNT5B	ENST00000861256.1		c.-57-6194C>G		intron	N/A	ENSP00000531315.1

Frequencies

GnomAD3 genomes AF: 0.527 AC: 79876 AN: 151580 Hom.: 21328 Cov.: 30

Gnomad AFR AF: 0.515

Gnomad AMI AF: 0.448

Gnomad AMR AF: 0.436

Gnomad ASJ AF: 0.579

Gnomad EAS AF: 0.425

Gnomad SAS AF: 0.512

Gnomad FIN AF: 0.523

Gnomad MID AF: 0.437

Gnomad NFE AF: 0.563

Gnomad OTH AF: 0.540

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

GnomAD4 genome AF: 0.527 AC: 79938 AN: 151700 Hom.: 21346 Cov.: 30 AF XY: 0.523 AC XY: 38730 AN XY: 74092

African (AFR) AF: 0.515 AC: 21297 AN: 41334

American (AMR) AF: 0.435 AC: 6632 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.579 AC: 2008 AN: 3468

East Asian (EAS) AF: 0.425 AC: 2192 AN: 5160

South Asian (SAS) AF: 0.511 AC: 2457 AN: 4808

European-Finnish (FIN) AF: 0.523 AC: 5475 AN: 10476

Middle Eastern (MID) AF: 0.429 AC: 126 AN: 294

European-Non Finnish (NFE) AF: 0.563 AC: 38207 AN: 67904

Other (OTH) AF: 0.540 AC: 1136 AN: 2104

Alfa AF: 0.535 Hom.: 2643

Bravo AF: 0.515

Asia WGS AF: 0.468 AC: 1630 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.0
DANN	Benign	0.45
PhyloP100		0.64
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: rs4766398; hg19: chr12-1734270;