ENST00000472238.1:n.337+150C>T

Variant names:

• chr3-55497239-G-A
• rs557077
• ENST00000472238.1:n.337+150C>T

Variant summary

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

The ENST00000472238.1(ENSG00000242317):​n.337+150C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.347 in 152,188 control chromosomes in the GnomAD database, including 12,422 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 0.35 (12419 hom., cov: 33)
  • Exomes 𝑓: 0.35 (3 hom.)
• Consequence: ENSG00000242317 ENST00000472238.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.489
• Publications: 9 publications found

Genes affected

ENSG00000242317 (HGNC:):

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.671 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000472238.1. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000242317	ENST00000472238.1	TSL:4	n.337+150C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.347 AC: 52785 AN: 152044 Hom.: 12405 Cov.: 33

Gnomad AFR AF: 0.679

Gnomad AMI AF: 0.241

Gnomad AMR AF: 0.282

Gnomad ASJ AF: 0.238

Gnomad EAS AF: 0.149

Gnomad SAS AF: 0.290

Gnomad FIN AF: 0.246

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.203

Gnomad OTH AF: 0.313

GnomAD4 exome AF: 0.346 AC: 9 AN: 26 Hom.: 3 AF XY: 0.444 AC XY: 8 AN XY: 18

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.450 AC: 9 AN: 20

Other (OTH) AF: 0.00 AC: 0 AN: 4

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0186682), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.347 AC: 52835 AN: 152162 Hom.: 12419 Cov.: 33 AF XY: 0.346 AC XY: 25739 AN XY: 74376

African (AFR) AF: 0.678 AC: 28149 AN: 41516

American (AMR) AF: 0.281 AC: 4303 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.238 AC: 827 AN: 3468

East Asian (EAS) AF: 0.150 AC: 774 AN: 5172

South Asian (SAS) AF: 0.289 AC: 1397 AN: 4828

European-Finnish (FIN) AF: 0.246 AC: 2598 AN: 10566

Middle Eastern (MID) AF: 0.316 AC: 93 AN: 294

European-Non Finnish (NFE) AF: 0.203 AC: 13822 AN: 68000

Other (OTH) AF: 0.308 AC: 652 AN: 2114

Alfa AF: 0.242 Hom.: 10939

Bravo AF: 0.366

Asia WGS AF: 0.261 AC: 906 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.13
DANN	Benign	0.39
PhyloP100		-0.49

Splicing

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

Other links and lift over

dbSNP: rs557077; hg19: chr3-55531267;