rs72882759

Variant names:

• chr2-47369005-C-G
• rs72882759
• ENST00000405271.5:c.-71C>G

Your query was ambiguous. Multiple possible variants found:

• chr2-47369005-C-G
• chr2-47369005-C-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000456133.5(EPCAM):​n.-71C>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0167 in 1,343,634 control chromosomes in the GnomAD database, including 739 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.045 (408 hom., cov: 32)
  • Exomes 𝑓: 0.013 (331 hom.)
• Consequence: EPCAM ENST00000456133.5 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.761
• Publications: 1 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 2-47369005-C-G is Benign according to our data. Variant chr2-47369005-C-G is described in ClinVar as Benign. ClinVar VariationId is 1224010.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.132 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000456133.5. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EPCAM	ENST00000405271.5	TSL:5	c.-71C>G		5_prime_UTR	Exon 2 of 10	ENSP00000385476.1	B5MCA4
	EPCAM	ENST00000456133.5	TSL:5	n.-71C>G		non_coding_transcript_exon	Exon 2 of 11	ENSP00000410675.1	B5MCA4
	EPCAM	ENST00000456133.5	TSL:5	n.-71C>G		5_prime_UTR	Exon 2 of 11	ENSP00000410675.1	B5MCA4

Frequencies

GnomAD3 genomes AF: 0.0447 AC: 6802 AN: 152076 Hom.: 405 Cov.: 32

Gnomad AFR AF: 0.135

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0176

Gnomad ASJ AF: 0.0147

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00455

Gnomad FIN AF: 0.00386

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0107

Gnomad OTH AF: 0.0344

GnomAD4 exome AF: 0.0131 AC: 15642 AN: 1191440 Hom.: 331 Cov.: 30 AF XY: 0.0128 AC XY: 7282 AN XY: 570444

African (AFR) AF: 0.142 AC: 3345 AN: 23496

American (AMR) AF: 0.0154 AC: 135 AN: 8762

Ashkenazi Jewish (ASJ) AF: 0.0151 AC: 250 AN: 16512

East Asian (EAS) AF: 0.0000748 AC: 2 AN: 26736

South Asian (SAS) AF: 0.00680 AC: 290 AN: 42620

European-Finnish (FIN) AF: 0.00352 AC: 144 AN: 40886

Middle Eastern (MID) AF: 0.0288 AC: 141 AN: 4904

European-Non Finnish (NFE) AF: 0.0106 AC: 10380 AN: 978614

Other (OTH) AF: 0.0195 AC: 955 AN: 48910

GnomAD4 genome AF: 0.0448 AC: 6824 AN: 152194 Hom.: 408 Cov.: 32 AF XY: 0.0427 AC XY: 3175 AN XY: 74432

African (AFR) AF: 0.135 AC: 5622 AN: 41512

American (AMR) AF: 0.0176 AC: 269 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0147 AC: 51 AN: 3470

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5156

South Asian (SAS) AF: 0.00456 AC: 22 AN: 4826

European-Finnish (FIN) AF: 0.00386 AC: 41 AN: 10614

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.0107 AC: 727 AN: 68006

Other (OTH) AF: 0.0336 AC: 71 AN: 2112

Alfa AF: 0.00396 Hom.: 1

Bravo AF: 0.0499

Asia WGS AF: 0.00837 AC: 30 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	1.5
DANN	Benign	0.47
PhyloP100		-0.76
PromoterAI		-0.039	Neutral
Mutation Taster		=300/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs72882759; hg19: chr2-47596144;