XM_047448853.1:c.-1967A>C

Variant names:

• chr3-55491957-T-G
• rs524153
• XM_047448853.1:c.-1967A>C

Variant summary

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

The XM_047448853.1(WNT5A):​c.-1967A>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.553 in 152,090 control chromosomes in the GnomAD database, including 24,114 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 0.55 (24114 hom., cov: 33)
• Consequence: WNT5A XM_047448853.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0410
• Publications: 5 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: G2P, Labcorp Genetics (formerly Invitae), Illumina, Ambry Genetics
• 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.698 is higher than 0.05.

Variant Effect in Transcripts

 

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Frequencies

GnomAD3 genomes AF: 0.553 AC: 83989 AN: 151972 Hom.: 24078 Cov.: 33

Gnomad AFR AF: 0.705

Gnomad AMI AF: 0.438

Gnomad AMR AF: 0.428

Gnomad ASJ AF: 0.540

Gnomad EAS AF: 0.337

Gnomad SAS AF: 0.599

Gnomad FIN AF: 0.532

Gnomad MID AF: 0.604

Gnomad NFE AF: 0.507

Gnomad OTH AF: 0.540

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

GnomAD4 genome AF: 0.553 AC: 84082 AN: 152090 Hom.: 24114 Cov.: 33 AF XY: 0.552 AC XY: 41028 AN XY: 74352

African (AFR) AF: 0.705 AC: 29233 AN: 41476

American (AMR) AF: 0.428 AC: 6547 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.540 AC: 1875 AN: 3472

East Asian (EAS) AF: 0.338 AC: 1738 AN: 5148

South Asian (SAS) AF: 0.601 AC: 2899 AN: 4822

European-Finnish (FIN) AF: 0.532 AC: 5626 AN: 10580

Middle Eastern (MID) AF: 0.616 AC: 181 AN: 294

European-Non Finnish (NFE) AF: 0.507 AC: 34452 AN: 67988

Other (OTH) AF: 0.537 AC: 1134 AN: 2110

Alfa AF: 0.452 Hom.: 2364

Bravo AF: 0.552

Asia WGS AF: 0.499 AC: 1738 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.62
DANN	Benign	0.36
PhyloP100		0.041

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs524153; hg19: chr3-55525985;