11-124924816-C-T

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.339G>A(p.Gln113Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.028 in 1,614,120 control chromosomes in the GnomAD database, including 875 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.031 ( 87 hom., cov: 32)

Exomes 𝑓: 0.028 ( 788 hom. )

Consequence

HEPACAM
NM_152722.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.71

Publications

6 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=-0.42).

BP6

Variant 11-124924816-C-T is Benign according to our data. Variant chr11-124924816-C-T is described in ClinVar as Benign. ClinVar VariationId is 262677.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.71 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0737 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
HEPACAM	NM_152722.5 link	c.339G>A	p.Gln113Gln	synonymous_variant	Exon 2 of 7	ENST00000298251.5	NP_689935.2
HEPACAM	NM_001411043.1 link	c.339G>A	p.Gln113Gln	synonymous_variant	Exon 2 of 7		NP_001397972.1
HEPACAM	NM_001441320.1 link	c.339G>A	p.Gln113Gln	synonymous_variant	Exon 2 of 7		NP_001428249.1
LOC107984406	XR_001748429.3 link	n.335-18584C>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.339G>A	p.Gln113Gln	synonymous_variant	Exon 2 of 7	1	NM_152722.5	ENSP00000298251.4

Frequencies

GnomAD3 genomes

AF:

0.0306

AC:

4659

AN:

152126

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0420

Gnomad AMI

AF:

0.0208

Gnomad AMR

AF:

0.0185

Gnomad ASJ

AF:

0.0608

Gnomad EAS

AF:

0.0799

Gnomad SAS

AF:

0.0621

Gnomad FIN

AF:

0.00697

Gnomad MID

AF:

0.0380

Gnomad NFE

AF:

0.0228

Gnomad OTH

AF:

0.0287

GnomAD2 exomes

AF:

0.0334

AC:

8388

AN:

251482

AF XY:

0.0347

show subpopulations

Gnomad AFR exome

AF:

0.0419

Gnomad AMR exome

AF:

0.0175

Gnomad ASJ exome

AF:

0.0608

Gnomad EAS exome

AF:

0.0919

Gnomad FIN exome

AF:

0.00827

Gnomad NFE exome

AF:

0.0238

Gnomad OTH exome

AF:

0.0279

GnomAD4 exome

AF:

0.0277

AC:

40472

AN:

1461876

Hom.:

788

Cov.:

AF XY:

0.0286

AC XY:

20834

AN XY:

727240

show subpopulations

African (AFR)

AF:

0.0443

AC:

1483

AN:

33480

American (AMR)

AF:

0.0175

AC:

784

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0610

AC:

1593

AN:

26136

East Asian (EAS)

AF:

0.0826

AC:

3279

AN:

39700

South Asian (SAS)

AF:

0.0547

AC:

4719

AN:

86254

European-Finnish (FIN)

AF:

0.00874

AC:

467

AN:

53416

Middle Eastern (MID)

AF:

0.0511

AC:

295

AN:

5768

European-Non Finnish (NFE)

AF:

0.0233

AC:

25916

AN:

1112002

Other (OTH)

AF:

0.0321

AC:

1936

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

2359

4718

7078

9437

11796

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1074

2148

3222

4296

5370

<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:

0.0306

AC:

4661

AN:

152244

Hom.:

Cov.:

AF XY:

0.0300

AC XY:

2235

AN XY:

74450

show subpopulations

African (AFR)

AF:

0.0420

AC:

1744

AN:

41520

American (AMR)

AF:

0.0185

AC:

283

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.0608

AC:

211

AN:

3468

East Asian (EAS)

AF:

0.0801

AC:

414

AN:

5168

South Asian (SAS)

AF:

0.0615

AC:

297

AN:

4830

European-Finnish (FIN)

AF:

0.00697

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.0340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0228

AC:

1549

AN:

68018

Other (OTH)

AF:

0.0284

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

237

473

710

946

1183

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

180

240

300

<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:

0.0276

Hom.:

151

Bravo

AF:

0.0327

Asia WGS

AF:

0.0460

AC:

162

AN:

3478

EpiCase

AF:

0.0220

EpiControl

AF:

0.0241

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

- -

Jan 27, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Oct 31, 2018

GeneDx

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

-0.42

CADD

Benign

7.7

(source)

DANN

Benign

0.87

PhyloP100

1.7

Mutation Taster

=99/1

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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