dbSNP rs3924917: EPCAM:c.903+529G>A (chr2-47385739-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_002354.3(EPCAM):c.903+529G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.475 in 151,958 control chromosomes in the GnomAD database, including 19,139 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 0.47 ( 19139 hom., cov: 33)

Consequence

EPCAM
NM_002354.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.836

Publications

8 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=-0.95).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.713 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EPCAM	NM_002354.3 link	c.903+529G>A		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.903+529G>A	intron_variant	Intron 8 of 8	1	NM_002354.3	ENSP00000263735.4	P16422
EPCAM	ENST00000405271.5 link	c.987+529G>A	intron_variant	Intron 9 of 9	5		ENSP00000385476.1	B5MCA4
EPCAM	ENST00000456133.5 link	n.987+529G>A	intron_variant	Intron 9 of 10	5		ENSP00000410675.1	B5MCA4

Frequencies

GnomAD3 genomes

AF:

0.474

AC:

72024

AN:

151840

Hom.:

19104

Cov.:

show subpopulations

Gnomad AFR

AF:

0.701

Gnomad AMI

AF:

0.262

Gnomad AMR

AF:

0.401

Gnomad ASJ

AF:

0.306

Gnomad EAS

AF:

0.733

Gnomad SAS

AF:

0.416

Gnomad FIN

AF:

0.483

Gnomad MID

AF:

0.326

Gnomad NFE

AF:

0.349

Gnomad OTH

AF:

0.444

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.475

AC:

72112

AN:

151958

Hom.:

19139

Cov.:

AF XY:

0.478

AC XY:

35475

AN XY:

74254

show subpopulations

African (AFR)

AF:

0.702

AC:

29075

AN:

41446

American (AMR)

AF:

0.401

AC:

6107

AN:

15232

Ashkenazi Jewish (ASJ)

AF:

0.306

AC:

1063

AN:

3470

East Asian (EAS)

AF:

0.733

AC:

3789

AN:

5172

South Asian (SAS)

AF:

0.416

AC:

2007

AN:

4822

European-Finnish (FIN)

AF:

0.483

AC:

5088

AN:

10538

Middle Eastern (MID)

AF:

0.327

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.349

AC:

23711

AN:

67960

Other (OTH)

AF:

0.444

AC:

937

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1760

3519

5279

7038

8798

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

616

1232

1848

2464

3080

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.387

Hom.:

40405

Bravo

AF:

0.480

Asia WGS

AF:

0.588

AC:

2043

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

0.098

(source)

DANN

Benign

0.72

PhyloP100

-0.84

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over