Variant 2-47369061-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The ENST00000405271.5(EPCAM):c.-15A>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 0.00212 in 1,372,606 control chromosomes in the GnomAD database, including 56 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0098 ( 30 hom., cov: 32)

Exomes 𝑓: 0.0012 ( 26 hom. )

Consequence

EPCAM
ENST00000405271.5 5_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.623

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=-0.82).

BP6

Variant 2-47369061-A-G is Benign according to our data. Variant chr2-47369061-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 1217191.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00978 (1488/152156) while in subpopulation AFR AF= 0.0321 (1335/41534). AF 95% confidence interval is 0.0307. There are 30 homozygotes in gnomad4. There are 684 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 30 Mitochondrial gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EPCAM	ENST00000405271.5 linkuse as main transcript	c.-15A>G		5_prime_UTR_variant	2/10	5		ENSP00000385476
EPCAM	ENST00000456133.5 linkuse as main transcript	c.-15A>G		5_prime_UTR_variant, NMD_transcript_variant	2/11	5		ENSP00000410675

Frequencies

GnomAD3 genomes

AF:

0.00977

AC:

1485

AN:

152038

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0322

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00583

Gnomad ASJ

AF:

0.000864

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000622

Gnomad FIN

AF:

0.0000944

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000368

Gnomad OTH

AF:

0.0144

GnomAD3 exomes

AF:

0.00108

AC:

AN:

25890

Hom.:

AF XY:

0.000659

AC XY:

AN XY:

13650

show subpopulations

Gnomad AFR exome

AF:

0.0345

Gnomad AMR exome

AF:

0.0112

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000880

Gnomad NFE exome

AF:

0.000283

Gnomad OTH exome

AF:

0.00217

GnomAD4 exome

AF:

0.00116

AC:

1421

AN:

1220450

Hom.:

Cov.:

AF XY:

0.00108

AC XY:

633

AN XY:

588678

show subpopulations

Gnomad4 AFR exome

AF:

0.0368

Gnomad4 AMR exome

AF:

0.00515

Gnomad4 ASJ exome

AF:

0.000342

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000102

Gnomad4 FIN exome

AF:

0.0000230

Gnomad4 NFE exome

AF:

0.000309

Gnomad4 OTH exome

AF:

0.00324

GnomAD4 genome

AF:

0.00978

AC:

1488

AN:

152156

Hom.:

Cov.:

AF XY:

0.00919

AC XY:

684

AN XY:

74398

show subpopulations

Gnomad4 AFR

AF:

0.0321

Gnomad4 AMR

AF:

0.00582

Gnomad4 ASJ

AF:

0.000864

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.0000944

Gnomad4 NFE

AF:

0.000368

Gnomad4 OTH

AF:

0.0142

Alfa

AF:

0.00644

Hom.:

Bravo

AF:

0.0116

Asia WGS

AF:

0.00318

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 26, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

1.2

DANN

Benign

0.32

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