rs62139669

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002354.3(EPCAM):c.904-12T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0389 in 1,591,436 control chromosomes in the GnomAD database, including 1,405 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.034 ( 124 hom., cov: 33)

Exomes 𝑓: 0.039 ( 1281 hom. )

Consequence

EPCAM
NM_002354.3 intron

Scores

Splicing: ADA: 0.00009840

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -1.60

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

Variant 2-47386560-T-C is Benign according to our data. Variant chr2-47386560-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 258645.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-47386560-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0584 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EPCAM	NM_002354.3 link	c.904-12T>C		intron_variant	Intron 8 of 8	ENST00000263735.9	NP_002345.2	P16422

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
EPCAM	ENST00000263735.9 link	c.904-12T>C	intron_variant	Intron 8 of 8	1	NM_002354.3	ENSP00000263735.4	P16422
EPCAM	ENST00000405271.5 link	c.988-12T>C	intron_variant	Intron 9 of 9	5		ENSP00000385476.1	B5MCA4
EPCAM	ENST00000456133.5 link	n.988-12T>C	intron_variant	Intron 9 of 10	5		ENSP00000410675.1	B5MCA4

Frequencies

GnomAD3 genomes

AF:

0.0343

AC:

5221

AN:

152190

Hom.:

123

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00825

Gnomad AMI

AF:

0.0395

Gnomad AMR

AF:

0.0617

Gnomad ASJ

AF:

0.0378

Gnomad EAS

AF:

0.000576

Gnomad SAS

AF:

0.0566

Gnomad FIN

AF:

0.0458

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0430

Gnomad OTH

AF:

0.0363

GnomAD3 exomes

AF:

0.0402

AC:

9992

AN:

248810

Hom.:

260

AF XY:

0.0411

AC XY:

5538

AN XY:

134594

show subpopulations

Gnomad AFR exome

AF:

0.00627

Gnomad AMR exome

AF:

0.0561

Gnomad ASJ exome

AF:

0.0419

Gnomad EAS exome

AF:

0.000437

Gnomad SAS exome

AF:

0.0634

Gnomad FIN exome

AF:

0.0467

Gnomad NFE exome

AF:

0.0391

Gnomad OTH exome

AF:

0.0392

GnomAD4 exome

AF:

0.0394

AC:

56676

AN:

1439128

Hom.:

1281

Cov.:

AF XY:

0.0403

AC XY:

28826

AN XY:

716108

show subpopulations

Gnomad4 AFR exome

AF:

0.00530

Gnomad4 AMR exome

AF:

0.0548

Gnomad4 ASJ exome

AF:

0.0399

Gnomad4 EAS exome

AF:

0.000228

Gnomad4 SAS exome

AF:

0.0648

Gnomad4 FIN exome

AF:

0.0445

Gnomad4 NFE exome

AF:

0.0391

Gnomad4 OTH exome

AF:

0.0377

GnomAD4 genome

AF:

0.0343

AC:

5222

AN:

152308

Hom.:

124

Cov.:

AF XY:

0.0361

AC XY:

2686

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.00823

Gnomad4 AMR

AF:

0.0616

Gnomad4 ASJ

AF:

0.0378

Gnomad4 EAS

AF:

0.000578

Gnomad4 SAS

AF:

0.0570

Gnomad4 FIN

AF:

0.0458

Gnomad4 NFE

AF:

0.0430

Gnomad4 OTH

AF:

0.0360

Alfa

AF:

0.0396

Hom.:

Bravo

AF:

0.0318

Asia WGS

AF:

0.0220

AC:

AN:

3472

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Mar 04, 2025

Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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

- -

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Lynch syndrome 8

Benign:1

Jul 07, 2023

KCCC/NGS Laboratory, Kuwait Cancer Control Center

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

-0.78

CADD

Benign

2.6

DANN

Benign

0.81

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000098

dbscSNV1_RF

Benign

0.0

SpliceAI score (max)

0.040

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over