dbSNP rs58450758: EPCAM:c.555+650C>T (chr2-47377727-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002354.3(EPCAM):c.555+650C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.126 in 433,168 control chromosomes in the GnomAD database, including 4,793 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.17 ( 2925 hom., cov: 30)

Exomes 𝑓: 0.10 ( 1868 hom. )

Consequence

EPCAM
NM_002354.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.641

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:

MIR559 (HGNC:32815): (microRNA 559) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

MIR559 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.325 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
EPCAM	NM_002354.3 link	c.555+650C>T	intron_variant	Intron 5 of 8	ENST00000263735.9	NP_002345.2	P16422
MIR559	NR_030286.1 link	n.53C>T	non_coding_transcript_exon_variant	Exon 1 of 1
MIR559	unassigned_transcript_347	n.*17C>T	downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EPCAM	ENST00000263735.9 link	c.555+650C>T		intron_variant	Intron 5 of 8	1	NM_002354.3	ENSP00000263735.4		P16422

Frequencies

GnomAD3 genomes

AF:

0.165

AC:

24999

AN:

151066

Hom.:

2913

Cov.:

show subpopulations

Gnomad AFR

AF:

0.330

Gnomad AMI

AF:

0.0639

Gnomad AMR

AF:

0.137

Gnomad ASJ

AF:

0.0694

Gnomad EAS

AF:

0.194

Gnomad SAS

AF:

0.128

Gnomad FIN

AF:

0.153

Gnomad MID

AF:

0.104

Gnomad NFE

AF:

0.0820

Gnomad OTH

AF:

0.143

GnomAD3 exomes

AF:

0.122

AC:

14566

AN:

119442

Hom.:

1182

AF XY:

0.116

AC XY:

7376

AN XY:

63680

show subpopulations

Gnomad AFR exome

AF:

0.337

Gnomad AMR exome

AF:

0.138

Gnomad ASJ exome

AF:

0.0609

Gnomad EAS exome

AF:

0.191

Gnomad SAS exome

AF:

0.104

Gnomad FIN exome

AF:

0.153

Gnomad NFE exome

AF:

0.0808

Gnomad OTH exome

AF:

0.0980

GnomAD4 exome

AF:

0.105

AC:

29535

AN:

281982

Hom.:

1868

Cov.:

AF XY:

0.104

AC XY:

16744

AN XY:

161754

show subpopulations

Gnomad4 AFR exome

AF:

0.323

Gnomad4 AMR exome

AF:

0.139

Gnomad4 ASJ exome

AF:

0.0592

Gnomad4 EAS exome

AF:

0.188

Gnomad4 SAS exome

AF:

0.106

Gnomad4 FIN exome

AF:

0.148

Gnomad4 NFE exome

AF:

0.0831

Gnomad4 OTH exome

AF:

0.105

GnomAD4 genome

AF:

0.166

AC:

25035

AN:

151186

Hom.:

2925

Cov.:

AF XY:

0.168

AC XY:

12401

AN XY:

73800

show subpopulations

Gnomad4 AFR

AF:

0.330

Gnomad4 AMR

AF:

0.137

Gnomad4 ASJ

AF:

0.0694

Gnomad4 EAS

AF:

0.194

Gnomad4 SAS

AF:

0.127

Gnomad4 FIN

AF:

0.153

Gnomad4 NFE

AF:

0.0820

Gnomad4 OTH

AF:

0.143

Alfa

AF:

0.110

Hom.:

725

Bravo

AF:

0.172

Asia WGS

AF:

0.187

AC:

650

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

3.6

DANN

Benign

0.17

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

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over