chr2-47369061-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

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

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.623
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 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_multiple_submitters_no_conflicts, 2 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 GnomAd4 at 30 Mitochondrial gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
EPCAMENST00000405271.5 linkuse as main transcriptc.-15A>G 5_prime_UTR_variant 2/105
EPCAMENST00000456133.5 linkuse as main transcriptc.-15A>G 5_prime_UTR_variant, NMD_transcript_variant 2/115

Frequencies

GnomAD3 genomes
AF:
0.00977
AC:
1485
AN:
152038
Hom.:
30
Cov.:
32
show subpopulations
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
show subpopulations
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
show subpopulations
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
show subpopulations
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
LINK: link

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingGeneDxJul 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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs78212572; hg19: chr2-47596200; API