rs648872

Positions:

• chr3-55485829-G-A
• chr3-55485829-G-C

Variant summary

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

The NM_003392.7(WNT5A):​c.6+1151C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.199 in 152,098 control chromosomes in the GnomAD database, including 3,363 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 0.20 (3363 hom., cov: 32)
• Consequence: WNT5A NM_003392.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.650

Genes affected

WNT5A (HGNC:12784): (Wnt family member 5A) 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 encodes a member of the WNT family that signals through both the canonical and non-canonical WNT pathways. This protein is a ligand for the seven transmembrane receptor frizzled-5 and the tyrosine kinase orphan receptor 2. This protein plays an essential role in regulating developmental pathways during embryogenesis. This protein may also play a role in oncogenesis. Mutations in this gene are the cause of autosomal dominant Robinow syndrome. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Jan 2012]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.286 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WNT5A	NM_003392.7	c.6+1151C>T		intron_variant		ENST00000264634.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WNT5A	ENST00000264634.9	c.6+1151C>T		intron_variant		1	NM_003392.7	P1
WNT5A	ENST00000474267.5	c.6+1151C>T		intron_variant		5		P1

Frequencies

GnomAD3 genomes AF: 0.199 AC: 30297 AN: 151980 Hom.: 3365 Cov.: 32

Gnomad AFR AF: 0.291

Gnomad AMI AF: 0.176

Gnomad AMR AF: 0.137

Gnomad ASJ AF: 0.226

Gnomad EAS AF: 0.0584

Gnomad SAS AF: 0.163

Gnomad FIN AF: 0.232

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.166

Gnomad OTH AF: 0.181

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

GnomAD4 genome AF: 0.199 AC: 30302 AN: 152098 Hom.: 3363 Cov.: 32 AF XY: 0.199 AC XY: 14804 AN XY: 74354

Gnomad4 AFR AF: 0.290

Gnomad4 AMR AF: 0.136

Gnomad4 ASJ AF: 0.226

Gnomad4 EAS AF: 0.0586

Gnomad4 SAS AF: 0.162

Gnomad4 FIN AF: 0.232

Gnomad4 NFE AF: 0.166

Gnomad4 OTH AF: 0.177

Alfa AF: 0.166 Hom.: 4505

Bravo AF: 0.196

Asia WGS AF: 0.123 AC: 428 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.0
DANN	Benign	0.64

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: rs648872; hg19: chr3-55519857;