rs7584256

chr2-47385085-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002354.3(EPCAM):c.859-81C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.283 in 1,011,288 control chromosomes in the GnomAD database, including 43,193 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.30 (7452 hom., cov: 33)
  • Exomes 𝑓: 0.28 (35741 hom.)
• Consequence: EPCAM NM_002354.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.653

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 2-47385085-C-T is Benign according to our data. Variant chr2-47385085-C-T is described in ClinVar as [Benign]. Clinvar id is 1225243.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.534 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EPCAM	NM_002354.3	c.859-81C>T		intron_variant		ENST00000263735.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EPCAM	ENST00000263735.9	c.859-81C>T		intron_variant		1	NM_002354.3	P1
EPCAM	ENST00000405271.5	c.943-81C>T		intron_variant		5
EPCAM	ENST00000456133.5	c.943-81C>T		intron_variant, NMD_transcript_variant		5
EPCAM	ENST00000490733.1	n.708-81C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.304 AC: 46205 AN: 151880 Hom.: 7447 Cov.: 33

Gnomad AFR AF: 0.354

Gnomad AMI AF: 0.237

Gnomad AMR AF: 0.267

Gnomad ASJ AF: 0.212

Gnomad EAS AF: 0.552

Gnomad SAS AF: 0.292

Gnomad FIN AF: 0.369

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.261

Gnomad OTH AF: 0.289

GnomAD4 exome AF: 0.279 AC: 239970 AN: 859290 Hom.: 35741 AF XY: 0.278 AC XY: 125661 AN XY: 452144

Gnomad4 AFR exome AF: 0.357

Gnomad4 AMR exome AF: 0.247

Gnomad4 ASJ exome AF: 0.221

Gnomad4 EAS exome AF: 0.519

Gnomad4 SAS exome AF: 0.278

Gnomad4 FIN exome AF: 0.372

Gnomad4 NFE exome AF: 0.257

Gnomad4 OTH exome AF: 0.292

GnomAD4 genome AF: 0.304 AC: 46254 AN: 151998 Hom.: 7452 Cov.: 33 AF XY: 0.308 AC XY: 22867 AN XY: 74274

Gnomad4 AFR AF: 0.354

Gnomad4 AMR AF: 0.267

Gnomad4 ASJ AF: 0.212

Gnomad4 EAS AF: 0.551

Gnomad4 SAS AF: 0.293

Gnomad4 FIN AF: 0.369

Gnomad4 NFE AF: 0.261

Gnomad4 OTH AF: 0.288

Alfa AF: 0.277 Hom.: 2847

Bravo AF: 0.300

Asia WGS AF: 0.403 AC: 1398 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	1.1
Dann	Benign	0.44

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

LitVar

Other links and lift over

dbSNP: rs7584256; hg19: chr2-47612224; COSMIC: COSV55395062; COSMIC: COSV55395062;