rs371271353

Variant names:

• chr2-47369259-G-C
• rs371271353
• ENST00000934495.1:c.-247G>C

Your query was ambiguous. Multiple possible variants found:

• chr2-47369259-G-C
• chr2-47369259-G-A
• chr2-47369259-G-T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The ENST00000934495.1(EPCAM):​c.-247G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000833 in 1,440,218 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00065 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00085 (19 hom.)
• Consequence: EPCAM ENST00000934495.1 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.304
• Publications: 0 publications found

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

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BP6: Variant 2-47369259-G-C is Benign according to our data. Variant chr2-47369259-G-C is described in ClinVar as Likely_benign. ClinVar VariationId is 336399.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00065 (99/152340) while in subpopulation SAS AF = 0.0201 (97/4834). AF 95% confidence interval is 0.0168. There are 0 homozygotes in GnomAd4. There are 63 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 19 AD,AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000934495.1. 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.-247G>C		upstream_gene	N/A	NP_002345.2	P16422

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EPCAM	ENST00000934495.1		c.-247G>C		5_prime_UTR	Exon 1 of 8	ENSP00000604554.1
	EPCAM	ENST00000405271.5	TSL:5	c.160+24G>C		intron	N/A	ENSP00000385476.1	B5MCA4
	EPCAM	ENST00000456133.5	TSL:5	n.160+24G>C		intron	N/A	ENSP00000410675.1	B5MCA4

Frequencies

GnomAD3 genomes AF: 0.000650 AC: 99 AN: 152226 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0200

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.00369 AC: 181 AN: 49090 AF XY: 0.00467

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000257

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000854 AC: 1100 AN: 1287878 Hom.: 19 Cov.: 30 AF XY: 0.00118 AC XY: 745 AN XY: 633752

African (AFR) AF: 0.0000400 AC: 1 AN: 24986

American (AMR) AF: 0.0000709 AC: 1 AN: 14102

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22228

East Asian (EAS) AF: 0.000179 AC: 5 AN: 27962

South Asian (SAS) AF: 0.0154 AC: 1004 AN: 65234

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32926

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3878

European-Non Finnish (NFE) AF: 0.00000479 AC: 5 AN: 1042876

Other (OTH) AF: 0.00156 AC: 84 AN: 53686

GnomAD4 genome AF: 0.000650 AC: 99 AN: 152340 Hom.: 0 Cov.: 32 AF XY: 0.000846 AC XY: 63 AN XY: 74486

African (AFR) AF: 0.0000240 AC: 1 AN: 41584

American (AMR) AF: 0.00 AC: 0 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.0201 AC: 97 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68024

Other (OTH) AF: 0.000473 AC: 1 AN: 2114

Alfa AF: 0.000347 Hom.: 0

Bravo AF: 0.000132

Asia WGS AF: 0.0180 AC: 61 AN: 3476

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	14
DANN	Benign	0.83
PhyloP100		0.30
PromoterAI		-0.016	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=297/3	polymorphism

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

Other links and lift over

dbSNP: rs371271353; hg19: chr2-47596398;