rs112686308

Variant names:

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_152722.5(HEPACAM):c.363G>A(p.Glu121Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0396 in 1,614,042 control chromosomes in the GnomAD database, including 1,480 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.028 ( 72 hom., cov: 32)

Exomes 𝑓: 0.041 ( 1408 hom. )

Consequence

HEPACAM
NM_152722.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.0110

Variant links:

Genes affected

HEPACAM (HGNC:26361): (hepatic and glial cell adhesion molecule) The protein encoded by this gene is a single-pass type I membrane protein that localizes to the cytoplasmic side of the cell membrane. The encoded protein acts as a homodimer and is involved in cell motility and cell-matrix interactions. The expression of this gene is downregulated or undetectable in many cancer cell lines, so this may be a tumor suppressor gene. [provided by RefSeq, Jul 2011]

HEPACAM links:

LOC107984406 (HGNC:):

LOC107984406 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.39).

BP6

Variant 11-124924792-C-T is Benign according to our data. Variant chr11-124924792-C-T is described in ClinVar as [Benign]. Clinvar id is 262678.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.011 with no splicing effect.

BA1

GnomAdExome4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.051 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HEPACAM	NM_152722.5 link	c.363G>A	p.Glu121Glu	synonymous_variant	Exon 2 of 7	ENST00000298251.5	NP_689935.2	Q14CZ8-1
HEPACAM	NM_001411043.1 link	c.363G>A	p.Glu121Glu	synonymous_variant	Exon 2 of 7		NP_001397972.1
HEPACAM	XM_005271449.3 link	c.363G>A	p.Glu121Glu	synonymous_variant	Exon 2 of 7		XP_005271506.1
LOC107984406	XR_001748429.3 link	n.335-18608C>T		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
HEPACAM	ENST00000298251.5 link	c.363G>A	p.Glu121Glu	synonymous_variant	Exon 2 of 7	1	NM_152722.5	ENSP00000298251.4	Q14CZ8-1
HEPACAM	ENST00000703807.1 link	c.363G>A	p.Glu121Glu	synonymous_variant	Exon 2 of 7			ENSP00000515485.1	A0A994J4I1
HEPACAM	ENST00000526273.1 link	n.135G>A		non_coding_transcript_exon_variant	Exon 1 of 2	2
HEPACAM	ENST00000528971.1 link	n.769G>A		non_coding_transcript_exon_variant	Exon 2 of 2	2

Frequencies

GnomAD3 genomes

AF:

0.0280

AC:

4257

AN:

152080

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00821

Gnomad AMI

AF:

0.0406

Gnomad AMR

AF:

0.0214

Gnomad ASJ

AF:

0.0135

Gnomad EAS

AF:

0.000578

Gnomad SAS

AF:

0.0465

Gnomad FIN

AF:

0.0173

Gnomad MID

AF:

0.0318

Gnomad NFE

AF:

0.0447

Gnomad OTH

AF:

0.0206

GnomAD3 exomes

AF:

0.0302

AC:

7594

AN:

251432

Hom.:

172

AF XY:

0.0331

AC XY:

4503

AN XY:

135898

show subpopulations

Gnomad AFR exome

AF:

0.00714

Gnomad AMR exome

AF:

0.0115

Gnomad ASJ exome

AF:

0.0147

Gnomad EAS exome

AF:

0.000326

Gnomad SAS exome

AF:

0.0520

Gnomad FIN exome

AF:

0.0205

Gnomad NFE exome

AF:

0.0415

Gnomad OTH exome

AF:

0.0282

GnomAD4 exome

AF:

0.0409

AC:

59724

AN:

1461844

Hom.:

1408

Cov.:

AF XY:

0.0415

AC XY:

30216

AN XY:

727228

show subpopulations

Gnomad4 AFR exome

AF:

0.00570

Gnomad4 AMR exome

AF:

0.0127

Gnomad4 ASJ exome

AF:

0.0143

Gnomad4 EAS exome

AF:

0.000126

Gnomad4 SAS exome

AF:

0.0523

Gnomad4 FIN exome

AF:

0.0204

Gnomad4 NFE exome

AF:

0.0453

Gnomad4 OTH exome

AF:

0.0409

GnomAD4 genome

AF:

0.0279

AC:

4253

AN:

152198

Hom.:

Cov.:

AF XY:

0.0274

AC XY:

2043

AN XY:

74428

show subpopulations

Gnomad4 AFR

AF:

0.00819

Gnomad4 AMR

AF:

0.0214

Gnomad4 ASJ

AF:

0.0135

Gnomad4 EAS

AF:

0.000580

Gnomad4 SAS

AF:

0.0465

Gnomad4 FIN

AF:

0.0173

Gnomad4 NFE

AF:

0.0447

Gnomad4 OTH

AF:

0.0204

Alfa

AF:

0.0359

Hom.:

Bravo

AF:

0.0260

Asia WGS

AF:

0.0180

AC:

AN:

3478

EpiCase

AF:

0.0457

EpiControl

AF:

0.0413

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Aug 03, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 30, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Megalencephalic leukoencephalopathy with subcortical cysts

Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.39

CADD

Benign

8.4

DANN

Benign

0.87

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

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

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over