rs114241106

Variant names:

• chr2-47373452-T-A
• rs114241106
• NM_002354.3:c.77-11T>A

Your query was ambiguous. Multiple possible variants found:

• chr2-47373452-T-A
• chr2-47373452-T-C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_002354.3(EPCAM):​c.77-11T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00976 in 1,571,516 control chromosomes in the GnomAD database, including 106 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0073 (9 hom., cov: 32)
  • Exomes 𝑓: 0.010 (97 hom.)
• Consequence: EPCAM NM_002354.3 intron
• Scores: Splicing: ADA: 0.01286
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -1.89
• Publications: 2 publications found

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]

EPCAM Gene-Disease associations (from GenCC):

• Lynch syndrome

  Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
• Lynch syndrome 8

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, G2P, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
• congenital diarrhea 5 with tufting enteropathy

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia, Orphanet, G2P, Ambry Genetics
• hereditary breast carcinoma

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 2-47373452-T-A is Benign according to our data. Variant chr2-47373452-T-A is described in ClinVar as Benign. ClinVar VariationId is 137214.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00732 (1114/152224) while in subpopulation NFE AF = 0.011 (747/68022). AF 95% confidence interval is 0.0103. There are 9 homozygotes in GnomAd4. There are 492 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 9 AR,AD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EPCAM	NM_002354.3	c.77-11T>A		intron_variant	Intron 1 of 8	ENST00000263735.9	NP_002345.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EPCAM	ENST00000263735.9	c.77-11T>A		intron_variant	Intron 1 of 8	1	NM_002354.3	ENSP00000263735.4

Frequencies

GnomAD3 genomes AF: 0.00734 AC: 1116 AN: 152106 Hom.: 9 Cov.: 32

Gnomad AFR AF: 0.00307

Gnomad AMI AF: 0.00659

Gnomad AMR AF: 0.00492

Gnomad ASJ AF: 0.0153

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00622

Gnomad FIN AF: 0.00396

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0110

Gnomad OTH AF: 0.00909

GnomAD2 exomes AF: 0.00810 AC: 1963 AN: 242328 AF XY: 0.00848

Gnomad AFR exome AF: 0.00209

Gnomad AMR exome AF: 0.00511

Gnomad ASJ exome AF: 0.0139

Gnomad EAS exome AF: 0.0000561

Gnomad FIN exome AF: 0.00438

Gnomad NFE exome AF: 0.0112

Gnomad OTH exome AF: 0.0102

GnomAD4 exome AF: 0.0100 AC: 14228 AN: 1419292 Hom.: 97 Cov.: 27 AF XY: 0.0101 AC XY: 7177 AN XY: 708394

African (AFR) AF: 0.00209 AC: 68 AN: 32466

American (AMR) AF: 0.00531 AC: 236 AN: 44444

Ashkenazi Jewish (ASJ) AF: 0.0151 AC: 390 AN: 25886

East Asian (EAS) AF: 0.0000764 AC: 3 AN: 39254

South Asian (SAS) AF: 0.00938 AC: 795 AN: 84766

European-Finnish (FIN) AF: 0.00354 AC: 183 AN: 51762

Middle Eastern (MID) AF: 0.0256 AC: 146 AN: 5702

European-Non Finnish (NFE) AF: 0.0109 AC: 11737 AN: 1076216

Other (OTH) AF: 0.0114 AC: 670 AN: 58796

GnomAD4 genome AF: 0.00732 AC: 1114 AN: 152224 Hom.: 9 Cov.: 32 AF XY: 0.00661 AC XY: 492 AN XY: 74434

African (AFR) AF: 0.00306 AC: 127 AN: 41538

American (AMR) AF: 0.00491 AC: 75 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0153 AC: 53 AN: 3468

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5182

South Asian (SAS) AF: 0.00601 AC: 29 AN: 4822

European-Finnish (FIN) AF: 0.00396 AC: 42 AN: 10598

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.0110 AC: 747 AN: 68022

Other (OTH) AF: 0.00852 AC: 18 AN: 2112

Alfa AF: 0.0103 Hom.: 1

Bravo AF: 0.00759

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:4

-

Genome Diagnostics Laboratory, Amsterdam University Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Dec 12, 2013

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Oct 03, 2016

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Clinical Genetics Laboratory, Department of Pathology, Netherlands Cancer Institute

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

EPCAM: BS1, BS2 -

Hereditary cancer-predisposing syndrome Benign:1

Dec 21, 2015

Vantari Genetics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.014
DANN	Benign	0.40
PhyloP100		-1.9
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.013
dbscSNV1_RF	Benign	0.23
SpliceAI score (max)		0.0		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: rs114241106; hg19: chr2-47600591; COSMIC: COSV104560662;