Genetic Variant ENST00000405271:c.-71C>G (chr2-47369005-C-G) – ACMG Classification: Benign (-20 pts)

Variant summary

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

The ENST00000405271(EPCAM):c.-71C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0167 in 1,343,634 control chromosomes in the GnomAD database, including 739 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.045 ( 408 hom., cov: 32)

Exomes 𝑓: 0.013 ( 331 hom. )

Consequence

EPCAM
ENST00000405271 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.761

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=-0.79).

BP6

Variant 2-47369005-C-G is Benign according to our data. Variant chr2-47369005-C-G is described in ClinVar as [Benign]. Clinvar id is 1224010.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.132 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein	UniProt
EPCAM	ENST00000405271 link	c.-71C>G	5_prime_UTR_variant	Exon 2 of 10	5	ENSP00000385476.1	B5MCA4
EPCAM	ENST00000456133.5 link	n.-71C>G	non_coding_transcript_exon_variant	Exon 2 of 11	5	ENSP00000410675.1	B5MCA4
EPCAM	ENST00000456133.5 link	n.-71C>G	5_prime_UTR_variant	Exon 2 of 11	5	ENSP00000410675.1	B5MCA4

Frequencies

GnomAD3 genomes

AF:

0.0447

AC:

6802

AN:

152076

Hom.:

405

Cov.:

show subpopulations

Gnomad AFR

AF:

0.135

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0176

Gnomad ASJ

AF:

0.0147

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00455

Gnomad FIN

AF:

0.00386

Gnomad MID

AF:

0.0633

Gnomad NFE

AF:

0.0107

Gnomad OTH

AF:

0.0344

GnomAD4 exome

AF:

0.0131

AC:

15642

AN:

1191440

Hom.:

331

Cov.:

AF XY:

0.0128

AC XY:

7282

AN XY:

570444

show subpopulations

Gnomad4 AFR exome

AF:

0.142

Gnomad4 AMR exome

AF:

0.0154

Gnomad4 ASJ exome

AF:

0.0151

Gnomad4 EAS exome

AF:

0.0000748

Gnomad4 SAS exome

AF:

0.00680

Gnomad4 FIN exome

AF:

0.00352

Gnomad4 NFE exome

AF:

0.0106

Gnomad4 OTH exome

AF:

0.0195

GnomAD4 genome

AF:

0.0448

AC:

6824

AN:

152194

Hom.:

408

Cov.:

AF XY:

0.0427

AC XY:

3175

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.135

Gnomad4 AMR

AF:

0.0176

Gnomad4 ASJ

AF:

0.0147

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.00456

Gnomad4 FIN

AF:

0.00386

Gnomad4 NFE

AF:

0.0107

Gnomad4 OTH

AF:

0.0336

Alfa

AF:

0.00396

Hom.:

Bravo

AF:

0.0499

Asia WGS

AF:

0.00837

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jun 15, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

1.5

DANN

Benign

0.47

Splicing

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