rs112686308

Variant names:

Variant summary

Our verdict is Benign. The variant received -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

Publications

9 publications found

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 Gene-Disease associations (from GenCC):

megalencephalic leukoencephalopathy with subcortical cysts 2B, remitting, with or without intellectual disability
Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, ClinGen, Labcorp Genetics (formerly Invitae)
megalencephalic leukoencephalopathy with subcortical cysts 2A
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, ClinGen, Labcorp Genetics (formerly Invitae)
macrocephaly-autism syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
megalencephalic leukoencephalopathy with subcortical cysts
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

HEPACAM links:

ENSG00000254943 (HGNC:):

ENSG00000254943 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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	NM_001441320.1 link	c.363G>A	p.Glu121Glu	synonymous_variant	Exon 2 of 7		NP_001428249.1
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	Appris	UniProt
HEPACAM	ENST00000298251.5 link	c.363G>A	p.Glu121Glu	synonymous_variant	Exon 2 of 7	1	NM_152722.5	ENSP00000298251.4		Q14CZ8-1

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

GnomAD2 exomes

AF:

0.0302

AC:

7594

AN:

251432

AF XY:

0.0331

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 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

African (AFR)

AF:

0.00570

AC:

191

AN:

33480

American (AMR)

AF:

0.0127

AC:

568

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0143

AC:

375

AN:

26136

East Asian (EAS)

AF:

0.000126

AC:

AN:

39700

South Asian (SAS)

AF:

0.0523

AC:

4512

AN:

86256

European-Finnish (FIN)

AF:

0.0204

AC:

1088

AN:

53414

Middle Eastern (MID)

AF:

0.0333

AC:

192

AN:

5768

European-Non Finnish (NFE)

AF:

0.0453

AC:

50325

AN:

1111970

Other (OTH)

AF:

0.0409

AC:

2468

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

3311

6622

9933

13244

16555

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1848

3696

5544

7392

9240

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0279

AC:

4253

AN:

152198

Hom.:

Cov.:

AF XY:

0.0274

AC XY:

2043

AN XY:

74428

show subpopulations

African (AFR)

AF:

0.00819

AC:

340

AN:

41524

American (AMR)

AF:

0.0214

AC:

327

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.0135

AC:

AN:

3470

East Asian (EAS)

AF:

0.000580

AC:

AN:

5174

South Asian (SAS)

AF:

0.0465

AC:

224

AN:

4818

European-Finnish (FIN)

AF:

0.0173

AC:

183

AN:

10608

Middle Eastern (MID)

AF:

0.0274

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0447

AC:

3041

AN:

67992

Other (OTH)

AF:

0.0204

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

217

433

650

866

1083

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

116

174

232

290

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

Jan 30, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Aug 03, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

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

(source)

DANN

Benign

0.87

PhyloP100

0.011

Mutation Taster

=97/3

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over