rs114241106

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

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

Variant links:

COSMIC-nc: COSV104560662

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), Ambry Genetics, G2P, Orphanet
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 -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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002354.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EPCAM	NM_002354.3	MANE Select	c.77-11T>A		intron	N/A	NP_002345.2	P16422

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
EPCAM	ENST00000263735.9	TSL:1 MANE Select	c.77-11T>A	intron	N/A	ENSP00000263735.4	P16422
EPCAM	ENST00000405271.5	TSL:5	c.161-11T>A	intron	N/A	ENSP00000385476.1	B5MCA4
EPCAM	ENST00000895681.1		c.77-11T>A	intron	N/A	ENSP00000565740.1

Frequencies

GnomAD3 genomes

AF:

0.00734

AC:

1116

AN:

152106

Hom.:

Cov.:

show subpopulations

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

show subpopulations

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.:

Cov.:

AF XY:

0.0101

AC XY:

7177

AN XY:

708394

show subpopulations

African (AFR)

AF:

0.00209

AC:

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:

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.455

Heterozygous variant carriers

583

1167

1750

2334

2917

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

436

872

1308

1744

2180

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00732

AC:

1114

AN:

152224

Hom.:

Cov.:

AF XY:

0.00661

AC XY:

492

AN XY:

74434

show subpopulations

African (AFR)

AF:

0.00306

AC:

127

AN:

41538

American (AMR)

AF:

0.00491

AC:

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.0153

AC:

AN:

3468

East Asian (EAS)

AF:

0.000193

AC:

AN:

5182

South Asian (SAS)

AF:

0.00601

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00396

AC:

AN:

10598

Middle Eastern (MID)

AF:

0.0544

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0110

AC:

747

AN:

68022

Other (OTH)

AF:

0.00852

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

130

196

261

326

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.0103

Hom.:

Bravo

AF:

0.00759

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (4)

not provided (2)

Hereditary cancer-predisposing syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.014

(source)

DANN

Benign

0.40

PhyloP100

-1.9

Mutation Taster

=100/0

polymorphism

(source)

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

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over