rs472631

Variant names:

• chr3-55477647-G-A
• rs472631
• NM_003392.7:c.391+1667C>T

Your query was ambiguous. Multiple possible variants found:

• chr3-55477647-G-A
• chr3-55477647-G-C

Variant summary

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

The NM_003392.7(WNT5A):​c.391+1667C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.518 in 151,954 control chromosomes in the GnomAD database, including 20,842 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 0.52 (20842 hom., cov: 32)
• Consequence: WNT5A NM_003392.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.589
• Publications: 13 publications found

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]

WNT5A Gene-Disease associations (from GenCC):

• autosomal dominant Robinow syndrome 1

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Illumina, Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
• autosomal dominant Robinow syndrome

  Inheritance: AD Classification: MODERATE, SUPPORTIVE Submitted by: Orphanet, ClinGen

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.617 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003392.7. 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
	WNT5A	NM_003392.7	MANE Select	c.391+1667C>T		intron	N/A	NP_003383.4
	WNT5A	NM_001256105.1		c.346+1667C>T		intron	N/A	NP_001243034.1
	WNT5A	NM_001377271.1		c.346+1667C>T		intron	N/A	NP_001364200.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WNT5A	ENST00000264634.9	TSL:1 MANE Select	c.391+1667C>T		intron	N/A	ENSP00000264634.4
	WNT5A	ENST00000474267.5	TSL:5	c.391+1667C>T		intron	N/A	ENSP00000417310.1
	WNT5A	ENST00000497027.5	TSL:2	c.346+1667C>T		intron	N/A	ENSP00000420104.1

Frequencies

GnomAD3 genomes AF: 0.518 AC: 78587 AN: 151836 Hom.: 20817 Cov.: 32

Gnomad AFR AF: 0.623

Gnomad AMI AF: 0.394

Gnomad AMR AF: 0.407

Gnomad ASJ AF: 0.514

Gnomad EAS AF: 0.331

Gnomad SAS AF: 0.591

Gnomad FIN AF: 0.527

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.488

Gnomad OTH AF: 0.506

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

GnomAD4 genome AF: 0.518 AC: 78664 AN: 151954 Hom.: 20842 Cov.: 32 AF XY: 0.519 AC XY: 38542 AN XY: 74256

African (AFR) AF: 0.623 AC: 25802 AN: 41424

American (AMR) AF: 0.406 AC: 6210 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.514 AC: 1786 AN: 3472

East Asian (EAS) AF: 0.331 AC: 1712 AN: 5168

South Asian (SAS) AF: 0.593 AC: 2848 AN: 4802

European-Finnish (FIN) AF: 0.527 AC: 5556 AN: 10536

Middle Eastern (MID) AF: 0.561 AC: 165 AN: 294

European-Non Finnish (NFE) AF: 0.488 AC: 33163 AN: 67952

Other (OTH) AF: 0.504 AC: 1063 AN: 2110

Alfa AF: 0.491 Hom.: 78051

Bravo AF: 0.512

Asia WGS AF: 0.487 AC: 1696 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	13
DANN	Benign	0.55
PhyloP100		0.59
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: rs472631; hg19: chr3-55511675;