2-47386731-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002354.3(EPCAM):c.*118T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.122 in 794,348 control chromosomes in the GnomAD database, including 6,859 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 0.10 ( 1096 hom., cov: 33)

Exomes 𝑓: 0.13 ( 5763 hom. )

Consequence

EPCAM
NM_002354.3 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -0.0870

Publications

36 publications found

Variant links:

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

EPCAM links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.166 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EPCAM	NM_002354.3 link	c.*118T>C		3_prime_UTR_variant	Exon 9 of 9	ENST00000263735.9	NP_002345.2	P16422

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
EPCAM	ENST00000263735.9 link	c.*118T>C	3_prime_UTR_variant	Exon 9 of 9	1	NM_002354.3	ENSP00000263735.4	P16422
EPCAM	ENST00000456133.5 link	n.*118T>C	non_coding_transcript_exon_variant	Exon 10 of 11	5		ENSP00000410675.1	B5MCA4
EPCAM	ENST00000405271.5 link	c.*118T>C	3_prime_UTR_variant	Exon 10 of 10	5		ENSP00000385476.1	B5MCA4
EPCAM	ENST00000456133.5 link	n.*118T>C	3_prime_UTR_variant	Exon 10 of 11	5		ENSP00000410675.1	B5MCA4

Frequencies

GnomAD3 genomes

AF:

0.104

AC:

15822

AN:

152142

Hom.:

1098

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0266

Gnomad AMI

AF:

0.182

Gnomad AMR

AF:

0.145

Gnomad ASJ

AF:

0.0582

Gnomad EAS

AF:

0.176

Gnomad SAS

AF:

0.0629

Gnomad FIN

AF:

0.151

Gnomad MID

AF:

0.0475

Gnomad NFE

AF:

0.134

Gnomad OTH

AF:

0.107

GnomAD4 exome

AF:

0.126

AC:

80730

AN:

642088

Hom.:

5763

Cov.:

AF XY:

0.123

AC XY:

42268

AN XY:

343418

show subpopulations

African (AFR)

AF:

0.0239

AC:

416

AN:

17440

American (AMR)

AF:

0.154

AC:

5135

AN:

33412

Ashkenazi Jewish (ASJ)

AF:

0.0640

AC:

1213

AN:

18956

East Asian (EAS)

AF:

0.160

AC:

5610

AN:

35038

South Asian (SAS)

AF:

0.0562

AC:

3207

AN:

57018

European-Finnish (FIN)

AF:

0.148

AC:

7038

AN:

47676

Middle Eastern (MID)

AF:

0.0350

AC:

100

AN:

2856

European-Non Finnish (NFE)

AF:

0.136

AC:

54168

AN:

397424

Other (OTH)

AF:

0.119

AC:

3843

AN:

32268

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

3383

6765

10148

13530

16913

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.104

AC:

15825

AN:

152260

Hom.:

1096

Cov.:

AF XY:

0.105

AC XY:

7808

AN XY:

74436

show subpopulations

African (AFR)

AF:

0.0265

AC:

1101

AN:

41580

American (AMR)

AF:

0.145

AC:

2217

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.0582

AC:

202

AN:

3468

East Asian (EAS)

AF:

0.176

AC:

910

AN:

5184

South Asian (SAS)

AF:

0.0636

AC:

307

AN:

4830

European-Finnish (FIN)

AF:

0.151

AC:

1598

AN:

10572

Middle Eastern (MID)

AF:

0.0476

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.134

AC:

9083

AN:

68020

Other (OTH)

AF:

0.107

AC:

227

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

723

1446

2169

2892

3615

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.125

Hom.:

969

Bravo

AF:

0.101

Asia WGS

AF:

0.113

AC:

394

AN:

3474

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

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

- -

Mar 04, 2025

Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Jul 14, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 30461124) -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

EPCAM-related disorder

Benign:1

Mar 04, 2022

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Hereditary cancer-predisposing syndrome

Benign:1

Jan 30, 2020

Sema4, Sema4

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:curation

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

3.1

(source)

DANN

Benign

0.75

PhyloP100

-0.087

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

2-47386731-T-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over