rs58450758

Positions:

• chr2-47377727-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.641

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]

MIR559 (HGNC:):

ACMG classification

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	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EPCAM	NM_002354.3	c.555+650C>T		intron_variant		ENST00000263735.9	NP_002345.2
MIR559	NR_030286.1	n.53C>T		non_coding_transcript_exon_variant	1/1
MIR559	unassigned_transcript_347	n.*17C>T		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EPCAM	ENST00000263735.9	c.555+650C>T		intron_variant		1	NM_002354.3	ENSP00000263735.4

Frequencies

GnomAD3 genomes AF: 0.165 AC: 24999 AN: 151066 Hom.: 2913 Cov.: 30

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

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.: 0 AF XY: 0.104 AC XY: 16744 AN XY: 161754

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.: 30 AF XY: 0.168 AC XY: 12401 AN XY: 73800

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

Other links and lift over

dbSNP: rs58450758; hg19: chr2-47604866; COSMIC: COSV55394564; COSMIC: COSV55394564;