dbSNP rs10790716: HEPACAM:p.Arg206Arg (chr11-124923820-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_152722.5(HEPACAM):c.618C>T(p.Arg206Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.244 in 1,613,940 control chromosomes in the GnomAD database, including 51,719 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. R206R) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.20 ( 3579 hom., cov: 32)

Exomes 𝑓: 0.25 ( 48140 hom. )

Consequence

HEPACAM
NM_152722.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -6.89

Publications

17 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=-0.77).

BP6

Variant 11-124923820-G-A is Benign according to our data. Variant chr11-124923820-G-A is described in ClinVar as Benign. ClinVar VariationId is 262680.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-6.89 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.271 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152722.5. 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.618C>T	p.Arg206Arg	synonymous	Exon 3 of 7	NP_689935.2	Q14CZ8-1
HEPACAM	NM_001411043.1		c.618C>T	p.Arg206Arg	synonymous	Exon 3 of 7	NP_001397972.1	A0A994J4I1
HEPACAM	NM_001441320.1		c.618C>T	p.Arg206Arg	synonymous	Exon 3 of 7	NP_001428249.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HEPACAM	ENST00000298251.5	TSL:1 MANE Select	c.618C>T	p.Arg206Arg	synonymous	Exon 3 of 7	ENSP00000298251.4	Q14CZ8-1
HEPACAM	ENST00000872129.1		c.618C>T	p.Arg206Arg	synonymous	Exon 3 of 7	ENSP00000542188.1
HEPACAM	ENST00000703807.1		c.618C>T	p.Arg206Arg	synonymous	Exon 3 of 7	ENSP00000515485.1	A0A994J4I1

Frequencies

GnomAD3 genomes

AF:

0.204

AC:

31071

AN:

152078

Hom.:

3585

Cov.:

show subpopulations

Gnomad AFR

AF:

0.129

Gnomad AMI

AF:

0.290

Gnomad AMR

AF:

0.158

Gnomad ASJ

AF:

0.138

Gnomad EAS

AF:

0.0772

Gnomad SAS

AF:

0.112

Gnomad FIN

AF:

0.233

Gnomad MID

AF:

0.180

Gnomad NFE

AF:

0.275

Gnomad OTH

AF:

0.213

GnomAD2 exomes

AF:

0.198

AC:

49823

AN:

251344

AF XY:

0.201

show subpopulations

Gnomad AFR exome

AF:

0.123

Gnomad AMR exome

AF:

0.119

Gnomad ASJ exome

AF:

0.147

Gnomad EAS exome

AF:

0.0871

Gnomad FIN exome

AF:

0.233

Gnomad NFE exome

AF:

0.270

Gnomad OTH exome

AF:

0.200

GnomAD4 exome

AF:

0.249

AC:

363515

AN:

1461744

Hom.:

48140

Cov.:

AF XY:

0.246

AC XY:

178529

AN XY:

727176

show subpopulations

African (AFR)

AF:

0.115

AC:

3866

AN:

33480

American (AMR)

AF:

0.125

AC:

5609

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.142

AC:

3698

AN:

26134

East Asian (EAS)

AF:

0.0968

AC:

3841

AN:

39698

South Asian (SAS)

AF:

0.118

AC:

10185

AN:

86258

European-Finnish (FIN)

AF:

0.238

AC:

12715

AN:

53386

Middle Eastern (MID)

AF:

0.158

AC:

912

AN:

5768

European-Non Finnish (NFE)

AF:

0.278

AC:

308746

AN:

1111912

Other (OTH)

AF:

0.231

AC:

13943

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

15567

31134

46700

62267

77834

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10006

20012

30018

40024

50030

<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:

0.204

AC:

31061

AN:

152196

Hom.:

3579

Cov.:

AF XY:

0.198

AC XY:

14736

AN XY:

74432

show subpopulations

African (AFR)

AF:

0.128

AC:

5328

AN:

41524

American (AMR)

AF:

0.157

AC:

2407

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.138

AC:

479

AN:

3472

East Asian (EAS)

AF:

0.0772

AC:

400

AN:

5182

South Asian (SAS)

AF:

0.113

AC:

544

AN:

4826

European-Finnish (FIN)

AF:

0.233

AC:

2468

AN:

10596

Middle Eastern (MID)

AF:

0.167

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.275

AC:

18677

AN:

67990

Other (OTH)

AF:

0.211

AC:

445

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1262

2523

3785

5046

6308

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

332

664

996

1328

1660

<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:

0.238

Hom.:

8364

Bravo

AF:

0.195

EpiCase

AF:

0.265

EpiControl

AF:

0.257

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

not specified (2)

Megalencephalic leukoencephalopathy with subcortical cysts (1)

Megalencephalic leukoencephalopathy with subcortical cysts 2A (1)

Megalencephalic leukoencephalopathy with subcortical cysts 2B, remitting, with or without intellectual disability (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

0.23

(source)

DANN

Benign

0.86

PhyloP100

-6.9

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)

0.010

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over