dbSNP rs11826299: HEPACAM:c.877+14C>T (chr11-124922731-G-A) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001411043.1(HEPACAM):c.891C>T(p.Ala297Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.101 in 1,614,030 control chromosomes in the GnomAD database, including 10,075 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.15 ( 2292 hom., cov: 32)

Exomes 𝑓: 0.096 ( 7783 hom. )

Consequence

HEPACAM
NM_001411043.1 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.109

Publications

7 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: ClinGen, Ambry Genetics, 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.55).

BP6

Variant 11-124922731-G-A is Benign according to our data. Variant chr11-124922731-G-A is described in ClinVar as Benign. ClinVar VariationId is 262682.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.109 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.282 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001411043.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HEPACAM	NM_152722.5	MANE Select	c.877+14C>T		intron	N/A	NP_689935.2	Q14CZ8-1
HEPACAM	NM_001411043.1		c.891C>T	p.Ala297Ala	synonymous	Exon 5 of 7	NP_001397972.1	A0A994J4I1
HEPACAM	NM_001441320.1		c.877+14C>T		intron	N/A	NP_001428249.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HEPACAM	ENST00000298251.5	TSL:1 MANE Select	c.877+14C>T		intron	N/A	ENSP00000298251.4	Q14CZ8-1
HEPACAM	ENST00000872129.1		c.912C>T	p.Ala304Ala	synonymous	Exon 5 of 7	ENSP00000542188.1
HEPACAM	ENST00000703807.1		c.891C>T	p.Ala297Ala	synonymous	Exon 5 of 7	ENSP00000515485.1	A0A994J4I1

Frequencies

GnomAD3 genomes

AF:

0.147

AC:

22393

AN:

152098

Hom.:

2292

Cov.:

show subpopulations

Gnomad AFR

AF:

0.286

Gnomad AMI

AF:

0.181

Gnomad AMR

AF:

0.0921

Gnomad ASJ

AF:

0.116

Gnomad EAS

AF:

0.0523

Gnomad SAS

AF:

0.0813

Gnomad FIN

AF:

0.126

Gnomad MID

AF:

0.212

Gnomad NFE

AF:

0.0916

Gnomad OTH

AF:

0.129

GnomAD2 exomes

AF:

0.102

AC:

25772

AN:

251490

AF XY:

0.0992

show subpopulations

Gnomad AFR exome

AF:

0.297

Gnomad AMR exome

AF:

0.0615

Gnomad ASJ exome

AF:

0.113

Gnomad EAS exome

AF:

0.0593

Gnomad FIN exome

AF:

0.118

Gnomad NFE exome

AF:

0.0968

Gnomad OTH exome

AF:

0.103

GnomAD4 exome

AF:

0.0965

AC:

141027

AN:

1461814

Hom.:

7783

Cov.:

AF XY:

0.0956

AC XY:

69494

AN XY:

727218

show subpopulations

African (AFR)

AF:

0.299

AC:

10009

AN:

33480

American (AMR)

AF:

0.0663

AC:

2965

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.115

AC:

3005

AN:

26134

East Asian (EAS)

AF:

0.0709

AC:

2815

AN:

39698

South Asian (SAS)

AF:

0.0790

AC:

6813

AN:

86258

European-Finnish (FIN)

AF:

0.117

AC:

6259

AN:

53414

Middle Eastern (MID)

AF:

0.151

AC:

869

AN:

5768

European-Non Finnish (NFE)

AF:

0.0916

AC:

101850

AN:

1111944

Other (OTH)

AF:

0.107

AC:

6442

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

7752

15503

23255

31006

38758

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3840

7680

11520

15360

19200

<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:

0.147

AC:

22405

AN:

152216

Hom.:

2292

Cov.:

AF XY:

0.145

AC XY:

10824

AN XY:

74430

show subpopulations

African (AFR)

AF:

0.286

AC:

11868

AN:

41492

American (AMR)

AF:

0.0920

AC:

1407

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.116

AC:

403

AN:

3472

East Asian (EAS)

AF:

0.0523

AC:

271

AN:

5186

South Asian (SAS)

AF:

0.0810

AC:

391

AN:

4828

European-Finnish (FIN)

AF:

0.126

AC:

1334

AN:

10604

Middle Eastern (MID)

AF:

0.224

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0916

AC:

6231

AN:

68016

Other (OTH)

AF:

0.127

AC:

269

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

930

1859

2789

3718

4648

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

226

452

678

904

1130

<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:

0.111

Hom.:

1582

Bravo

AF:

0.154

Asia WGS

AF:

0.0750

AC:

262

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

Megalencephalic leukoencephalopathy with subcortical cysts (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.55

CADD

Benign

(source)

DANN

Benign

0.76

PhyloP100

0.11

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over