2-47385739-G-A

Position:

• chr2-47385739-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_002354.3(EPCAM):​c.903+529G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.475 in 151,958 control chromosomes in the GnomAD database, including 19,139 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in Lovd as Benign (no stars).

• Frequency: Genomes: 𝑓 0.47 (19139 hom., cov: 33)
• Consequence: EPCAM NM_002354.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.836

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 2-47385739-G-A is Benign according to our data. Variant chr2-47385739-G-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.713 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EPCAM	NM_002354.3	c.903+529G>A		intron_variant		ENST00000263735.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EPCAM	ENST00000263735.9	c.903+529G>A		intron_variant		1	NM_002354.3	P1
EPCAM	ENST00000405271.5	c.987+529G>A		intron_variant		5
EPCAM	ENST00000456133.5	c.987+529G>A		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.474 AC: 72024 AN: 151840 Hom.: 19104 Cov.: 33

Gnomad AFR AF: 0.701

Gnomad AMI AF: 0.262

Gnomad AMR AF: 0.401

Gnomad ASJ AF: 0.306

Gnomad EAS AF: 0.733

Gnomad SAS AF: 0.416

Gnomad FIN AF: 0.483

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.349

Gnomad OTH AF: 0.444

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.475 AC: 72112 AN: 151958 Hom.: 19139 Cov.: 33 AF XY: 0.478 AC XY: 35475 AN XY: 74254

Gnomad4 AFR AF: 0.702

Gnomad4 AMR AF: 0.401

Gnomad4 ASJ AF: 0.306

Gnomad4 EAS AF: 0.733

Gnomad4 SAS AF: 0.416

Gnomad4 FIN AF: 0.483

Gnomad4 NFE AF: 0.349

Gnomad4 OTH AF: 0.444

Alfa AF: 0.372 Hom.: 16842

Bravo AF: 0.480

Asia WGS AF: 0.588 AC: 2043 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.098
DANN	Benign	0.72

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: rs3924917; hg19: chr2-47612878;