rs17036526

Variant names:

• chr2-47345224-G-C
• rs17036526
• ENST00000405271.5:c.-149+1G>C

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 2P and 8B. PVS1_Moderate BA1

The ENST00000405271.5(EPCAM):​c.-149+1G>C variant causes a splice donor, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.243 in 152,102 control chromosomes in the GnomAD database, including 5,239 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 0.24 (5239 hom., cov: 31)
  • Exomes 𝑓: 0.13 (0 hom.)
• Consequence: EPCAM ENST00000405271.5 splice_donor, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.634

Genes affected

EPCAM (HGNC:11529): (epithelial cell adhesion molecule) This gene encodes a carcinoma-associated antigen and is a member of a family that includes at least two type I membrane proteins. This antigen is expressed on most normal epithelial cells and gastrointestinal carcinomas and functions as a homotypic calcium-independent cell adhesion molecule. The antigen is being used as a target for immunotherapy treatment of human carcinomas. Mutations in this gene result in congenital tufting enteropathy. [provided by RefSeq, Dec 2008]

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• PVS1: Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 0.06413994 fraction of the gene. Cryptic splice site detected, with MaxEntScore 5.5, offset of -25, new splice context is: gggGTgagg. Cryptic site results in frameshift change. If cryptic site found is not functional and variant results in exon loss, it results in inframe change.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.38 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EPCAM	ENST00000405271.5	c.-149+1G>C		splice_donor_variant, intron_variant	Intron 1 of 9	5		ENSP00000385476.1
EPCAM	ENST00000456133.5	n.-149+1G>C		splice_donor_variant, intron_variant	Intron 1 of 10	5		ENSP00000410675.1

Frequencies

GnomAD3 genomes AF: 0.243 AC: 36882 AN: 151890 Hom.: 5224 Cov.: 31

Gnomad AFR AF: 0.385

Gnomad AMI AF: 0.126

Gnomad AMR AF: 0.192

Gnomad ASJ AF: 0.136

Gnomad EAS AF: 0.315

Gnomad SAS AF: 0.209

Gnomad FIN AF: 0.307

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.163

Gnomad OTH AF: 0.225

GnomAD4 exome AF: 0.128 AC: 12 AN: 94 Hom.: 0 Cov.: 0 AF XY: 0.125 AC XY: 8 AN XY: 64

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.131

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.243 AC: 36941 AN: 152008 Hom.: 5239 Cov.: 31 AF XY: 0.249 AC XY: 18471 AN XY: 74294

Gnomad4 AFR AF: 0.385

Gnomad4 AMR AF: 0.192

Gnomad4 ASJ AF: 0.136

Gnomad4 EAS AF: 0.315

Gnomad4 SAS AF: 0.209

Gnomad4 FIN AF: 0.307

Gnomad4 NFE AF: 0.163

Gnomad4 OTH AF: 0.222

Alfa AF: 0.204 Hom.: 441

Bravo AF: 0.243

Asia WGS AF: 0.288 AC: 999 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.33
CADD	Benign	19
DANN	Benign	0.91

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs17036526; hg19: chr2-47572363;