2-47369005-C-G

Position:

• chr2-47369005-C-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000405271.5(EPCAM):​c.-71C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0167 in 1,343,634 control chromosomes in the GnomAD database, including 739 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.045 (408 hom., cov: 32)
  • Exomes 𝑓: 0.013 (331 hom.)
• Consequence: EPCAM ENST00000405271.5 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.761

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 Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 2-47369005-C-G is Benign according to our data. Variant chr2-47369005-C-G is described in ClinVar as [Benign]. Clinvar id is 1224010.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.132 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EPCAM	ENST00000405271.5	c.-71C>G		5_prime_UTR_variant	2/10	5
EPCAM	ENST00000456133.5	c.-71C>G		5_prime_UTR_variant, NMD_transcript_variant	2/11	5

Frequencies

GnomAD3 genomes AF: 0.0447 AC: 6802 AN: 152076 Hom.: 405 Cov.: 32

Gnomad AFR AF: 0.135

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0176

Gnomad ASJ AF: 0.0147

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00455

Gnomad FIN AF: 0.00386

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0107

Gnomad OTH AF: 0.0344

GnomAD4 exome AF: 0.0131 AC: 15642 AN: 1191440 Hom.: 331 Cov.: 30 AF XY: 0.0128 AC XY: 7282 AN XY: 570444

Gnomad4 AFR exome AF: 0.142

Gnomad4 AMR exome AF: 0.0154

Gnomad4 ASJ exome AF: 0.0151

Gnomad4 EAS exome AF: 0.0000748

Gnomad4 SAS exome AF: 0.00680

Gnomad4 FIN exome AF: 0.00352

Gnomad4 NFE exome AF: 0.0106

Gnomad4 OTH exome AF: 0.0195

GnomAD4 genome AF: 0.0448 AC: 6824 AN: 152194 Hom.: 408 Cov.: 32 AF XY: 0.0427 AC XY: 3175 AN XY: 74432

Gnomad4 AFR AF: 0.135

Gnomad4 AMR AF: 0.0176

Gnomad4 ASJ AF: 0.0147

Gnomad4 EAS AF: 0.000194

Gnomad4 SAS AF: 0.00456

Gnomad4 FIN AF: 0.00386

Gnomad4 NFE AF: 0.0107

Gnomad4 OTH AF: 0.0336

Alfa AF: 0.00396 Hom.: 1

Bravo AF: 0.0499

Asia WGS AF: 0.00837 AC: 30 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 15, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	1.5
DANN	Benign	0.47

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs72882759; hg19: chr2-47596144;