rs504849

Variant names:

• chr3-55488911-T-C
• rs504849
• ENST00000474267.5:c.-414+926A>G

Your query was ambiguous. Multiple possible variants found:

• chr3-55488911-T-C
• chr3-55488911-T-G

Variant summary

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

The ENST00000474267.5(WNT5A):​c.-414+926A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.563 in 151,998 control chromosomes in the GnomAD database, including 25,488 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 0.56 (25488 hom., cov: 31)
• Consequence: WNT5A ENST00000474267.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.472
• Publications: 6 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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.763 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WNT5A	XM_017007127.2	c.48+21A>G		intron_variant	Intron 1 of 4		XP_016862616.1
WNT5A	XM_011534086.3	c.-40+1119A>G		intron_variant	Intron 6 of 9		XP_011532388.1
WNT5A	XM_017007128.2	c.-40+1119A>G		intron_variant	Intron 6 of 9		XP_016862617.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WNT5A	ENST00000474267.5	c.-414+926A>G		intron_variant	Intron 1 of 5	5		ENSP00000417310.1
WNT5A	ENST00000624674.1	n.*244A>G		downstream_gene_variant		5

Frequencies

GnomAD3 genomes AF: 0.563 AC: 85467 AN: 151880 Hom.: 25446 Cov.: 31

Gnomad AFR AF: 0.770

Gnomad AMI AF: 0.414

Gnomad AMR AF: 0.430

Gnomad ASJ AF: 0.501

Gnomad EAS AF: 0.337

Gnomad SAS AF: 0.594

Gnomad FIN AF: 0.521

Gnomad MID AF: 0.561

Gnomad NFE AF: 0.493

Gnomad OTH AF: 0.543

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

GnomAD4 genome AF: 0.563 AC: 85569 AN: 151998 Hom.: 25488 Cov.: 31 AF XY: 0.562 AC XY: 41768 AN XY: 74296

African (AFR) AF: 0.770 AC: 31946 AN: 41480

American (AMR) AF: 0.430 AC: 6571 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.501 AC: 1740 AN: 3470

East Asian (EAS) AF: 0.337 AC: 1735 AN: 5144

South Asian (SAS) AF: 0.597 AC: 2866 AN: 4804

European-Finnish (FIN) AF: 0.521 AC: 5514 AN: 10576

Middle Eastern (MID) AF: 0.575 AC: 168 AN: 292

European-Non Finnish (NFE) AF: 0.493 AC: 33517 AN: 67944

Other (OTH) AF: 0.541 AC: 1135 AN: 2098

Alfa AF: 0.464 Hom.: 1742

Bravo AF: 0.565

Asia WGS AF: 0.501 AC: 1743 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.1
DANN	Benign	0.40
PhyloP100		-0.47
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs504849; hg19: chr3-55522939;