2-47369061-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The ENST00000405271.5(EPCAM):c.-15A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00212 in 1,372,606 control chromosomes in the GnomAD database, including 56 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0098 (30 hom., cov: 32)
  • Exomes 𝑓: 0.0012 (26 hom.)
• Consequence: EPCAM ENST00000405271.5 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.623

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=-0.82).
• BP6: Variant 2-47369061-A-G is Benign according to our data. Variant chr2-47369061-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 1217191.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00978 (1488/152156) while in subpopulation AFR AF= 0.0321 (1335/41534). AF 95% confidence interval is 0.0307. There are 30 homozygotes in gnomad4. There are 684 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 30 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EPCAM	ENST00000405271.5	c.-15A>G		5_prime_UTR_variant	2/10	5
EPCAM	ENST00000456133.5	c.-15A>G		5_prime_UTR_variant, NMD_transcript_variant	2/11	5

Frequencies

GnomAD3 genomes AF: 0.00977 AC: 1485 AN: 152038 Hom.: 30 Cov.: 32

Gnomad AFR AF: 0.0322

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00583

Gnomad ASJ AF: 0.000864

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.0000944

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000368

Gnomad OTH AF: 0.0144

GnomAD3 exomes AF: 0.00108 AC: 28 AN: 25890 Hom.: 1 AF XY: 0.000659 AC XY: 9 AN XY: 13650

Gnomad AFR exome AF: 0.0345

Gnomad AMR exome AF: 0.0112

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000880

Gnomad NFE exome AF: 0.000283

Gnomad OTH exome AF: 0.00217

GnomAD4 exome AF: 0.00116 AC: 1421 AN: 1220450 Hom.: 26 Cov.: 30 AF XY: 0.00108 AC XY: 633 AN XY: 588678

Gnomad4 AFR exome AF: 0.0368

Gnomad4 AMR exome AF: 0.00515

Gnomad4 ASJ exome AF: 0.000342

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000102

Gnomad4 FIN exome AF: 0.0000230

Gnomad4 NFE exome AF: 0.000309

Gnomad4 OTH exome AF: 0.00324

GnomAD4 genome AF: 0.00978 AC: 1488 AN: 152156 Hom.: 30 Cov.: 32 AF XY: 0.00919 AC XY: 684 AN XY: 74398

Gnomad4 AFR AF: 0.0321

Gnomad4 AMR AF: 0.00582

Gnomad4 ASJ AF: 0.000864

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000622

Gnomad4 FIN AF: 0.0000944

Gnomad4 NFE AF: 0.000368

Gnomad4 OTH AF: 0.0142

Alfa AF: 0.00644 Hom.: 1

Bravo AF: 0.0116

Asia WGS AF: 0.00318 AC: 11 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 26, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	1.2
Dann	Benign	0.32

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs78212572; hg19: chr2-47596200;