chr11-124921418-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_152722.5(HEPACAM):c.971A>G(p.Asn324Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0408 in 1,270,318 control chromosomes in the GnomAD database, including 1,303 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.055 ( 293 hom., cov: 32)

Exomes 𝑓: 0.039 ( 1010 hom. )

Consequence

HEPACAM
NM_152722.5 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.624

Publications

2 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0013171732).

BP6

Variant 11-124921418-T-C is Benign according to our data. Variant chr11-124921418-T-C is described in ClinVar as Benign. ClinVar VariationId is 262683.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0905 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HEPACAM	NM_152722.5 link	c.971A>G	p.Asn324Ser	missense_variant	Exon 7 of 7	ENST00000298251.5	NP_689935.2	Q14CZ8-1
HEPACAM	NM_001411043.1 link	c.1127A>G	p.Asn376Ser	missense_variant	Exon 7 of 7		NP_001397972.1
HEPACAM	NM_001441320.1 link	c.968A>G	p.Asn323Ser	missense_variant	Exon 7 of 7		NP_001428249.1
LOC107984406	XR_001748429.3 link	n.335-21982T>C		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HEPACAM	ENST00000298251.5 link	c.971A>G	p.Asn324Ser	missense_variant	Exon 7 of 7	1	NM_152722.5	ENSP00000298251.4		Q14CZ8-1

Frequencies

GnomAD3 genomes

AF:

0.0549

AC:

8345

AN:

151884

Hom.:

291

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0928

Gnomad AMI

AF:

0.0286

Gnomad AMR

AF:

0.0502

Gnomad ASJ

AF:

0.0580

Gnomad EAS

AF:

0.0683

Gnomad SAS

AF:

0.0544

Gnomad FIN

AF:

0.0231

Gnomad MID

AF:

0.0475

Gnomad NFE

AF:

0.0371

Gnomad OTH

AF:

0.0584

GnomAD2 exomes

AF:

0.0217

AC:

299

AN:

13808

AF XY:

0.0221

show subpopulations

Gnomad AFR exome

AF:

0.0561

Gnomad AMR exome

AF:

0.0156

Gnomad ASJ exome

AF:

0.0390

Gnomad EAS exome

AF:

0.0464

Gnomad FIN exome

AF:

0.0150

Gnomad NFE exome

AF:

0.0175

Gnomad OTH exome

AF:

0.00585

GnomAD4 exome

AF:

0.0389

AC:

43470

AN:

1118320

Hom.:

1010

Cov.:

AF XY:

0.0387

AC XY:

20604

AN XY:

532976

show subpopulations

African (AFR)

AF:

0.0898

AC:

2118

AN:

23576

American (AMR)

AF:

0.0362

AC:

399

AN:

11018

Ashkenazi Jewish (ASJ)

AF:

0.0557

AC:

846

AN:

15178

East Asian (EAS)

AF:

0.0668

AC:

1821

AN:

27252

South Asian (SAS)

AF:

0.0435

AC:

1181

AN:

27164

European-Finnish (FIN)

AF:

0.0208

AC:

479

AN:

23010

Middle Eastern (MID)

AF:

0.0495

AC:

151

AN:

3052

European-Non Finnish (NFE)

AF:

0.0365

AC:

34382

AN:

942656

Other (OTH)

AF:

0.0461

AC:

2093

AN:

45414

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

2072

4144

6217

8289

10361

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1528

3056

4584

6112

7640

<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:

0.0550

AC:

8360

AN:

151998

Hom.:

293

Cov.:

AF XY:

0.0553

AC XY:

4108

AN XY:

74304

show subpopulations

African (AFR)

AF:

0.0930

AC:

3855

AN:

41456

American (AMR)

AF:

0.0502

AC:

768

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.0580

AC:

201

AN:

3464

East Asian (EAS)

AF:

0.0681

AC:

350

AN:

5140

South Asian (SAS)

AF:

0.0540

AC:

260

AN:

4814

European-Finnish (FIN)

AF:

0.0231

AC:

245

AN:

10584

Middle Eastern (MID)

AF:

0.0476

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0371

AC:

2519

AN:

67940

Other (OTH)

AF:

0.0578

AC:

122

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

428

855

1283

1710

2138

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

196

294

392

490

<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:

0.0423

Hom.:

113

Bravo

AF:

0.0578

TwinsUK

AF:

0.0343

AC:

127

ALSPAC

AF:

0.0324

AC:

125

ESP6500AA

AF:

0.0489

AC:

157

ESP6500EA

AF:

0.0226

AC:

154

ExAC

AF:

0.0153

AC:

1555

Asia WGS

AF:

0.0770

AC:

266

AN:

3478

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

- -

Jul 21, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 02, 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

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.73

CADD

Benign

8.8

(source)

DANN

Benign

0.47

DEOGEN2

Benign

0.0043

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.49

LIST_S2

Benign

0.59

MetaRNN

Benign

0.0013

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.34

PhyloP100

0.62

PrimateAI

Benign

0.39

PROVEAN

Benign

0.20

REVEL

Benign

0.035

Sift

Benign

0.22

Sift4G

Benign

0.71

Polyphen

0.0

Vest4

0.020

MPC

1.3

ClinPred

0.0083

GERP RS

-1.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.043

gMVP

0.13

Mutation Taster

=100/0

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