11-124923786-T-C

Position:

chr11-124923786-T-C

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 2P and 20B. PM1BP4_StrongBP6_Very_StrongBA1

The NM_152722.5(HEPACAM):c.652A>G(p.Met218Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.715 in 1,613,966 control chromosomes in the GnomAD database, including 415,256 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.76 ( 44418 hom., cov: 32)

Exomes 𝑓: 0.71 ( 370838 hom. )

Consequence

HEPACAM
NM_152722.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.220

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 links:

LOC107984406 (HGNC:):

LOC107984406 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

PM1

In a topological_domain Extracellular (size 206) in uniprot entity HECAM_HUMAN there are 11 pathogenic changes around while only 4 benign (73%) in NM_152722.5

BP4

Computational evidence support a benign effect (MetaRNN=1.1099867E-6).

BP6

Variant 11-124923786-T-C is Benign according to our data. Variant chr11-124923786-T-C is described in ClinVar as [Benign]. Clinvar id is 262681.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-124923786-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.88 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
HEPACAM	NM_152722.5 linkuse as main transcript	c.652A>G	p.Met218Val	missense_variant	3/7	ENST00000298251.5
LOC107984406	XR_001748429.3 linkuse as main transcript	n.335-19614T>C		intron_variant, non_coding_transcript_variant
HEPACAM	NM_001411043.1 linkuse as main transcript	c.652A>G	p.Met218Val	missense_variant	3/7
HEPACAM	XM_005271449.3 linkuse as main transcript	c.652A>G	p.Met218Val	missense_variant	3/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HEPACAM	ENST00000298251.5 linkuse as main transcript	c.652A>G	p.Met218Val	missense_variant	3/7	1	NM_152722.5	P1	Q14CZ8-1
HEPACAM	ENST00000703807.1 linkuse as main transcript	c.652A>G	p.Met218Val	missense_variant	3/7
HEPACAM	ENST00000526273.1 linkuse as main transcript	n.424A>G		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes

AF:

0.759

AC:

115386

AN:

152108

Hom.:

44366

Cov.:

show subpopulations

Gnomad AFR

AF:

0.875

Gnomad AMI

AF:

0.764

Gnomad AMR

AF:

0.674

Gnomad ASJ

AF:

0.638

Gnomad EAS

AF:

0.902

Gnomad SAS

AF:

0.749

Gnomad FIN

AF:

0.778

Gnomad MID

AF:

0.706

Gnomad NFE

AF:

0.700

Gnomad OTH

AF:

0.746

GnomAD3 exomes

AF:

0.722

AC:

181481

AN:

251320

Hom.:

66493

AF XY:

0.722

AC XY:

98113

AN XY:

135816

show subpopulations

Gnomad AFR exome

AF:

0.881

Gnomad AMR exome

AF:

0.607

Gnomad ASJ exome

AF:

0.639

Gnomad EAS exome

AF:

0.892

Gnomad SAS exome

AF:

0.746

Gnomad FIN exome

AF:

0.769

Gnomad NFE exome

AF:

0.700

Gnomad OTH exome

AF:

0.701

GnomAD4 exome

AF:

0.710

AC:

1037907

AN:

1461740

Hom.:

370838

Cov.:

AF XY:

0.711

AC XY:

516897

AN XY:

727170

show subpopulations

Gnomad4 AFR exome

AF:

0.879

Gnomad4 AMR exome

AF:

0.614

Gnomad4 ASJ exome

AF:

0.638

Gnomad4 EAS exome

AF:

0.910

Gnomad4 SAS exome

AF:

0.744

Gnomad4 FIN exome

AF:

0.766

Gnomad4 NFE exome

AF:

0.697

Gnomad4 OTH exome

AF:

0.722

GnomAD4 genome

AF:

0.759

AC:

115502

AN:

152226

Hom.:

44418

Cov.:

AF XY:

0.763

AC XY:

56781

AN XY:

74422

show subpopulations

Gnomad4 AFR

AF:

0.875

Gnomad4 AMR

AF:

0.674

Gnomad4 ASJ

AF:

0.638

Gnomad4 EAS

AF:

0.902

Gnomad4 SAS

AF:

0.750

Gnomad4 FIN

AF:

0.778

Gnomad4 NFE

AF:

0.700

Gnomad4 OTH

AF:

0.749

Alfa

AF:

0.710

Hom.:

63756

Bravo

AF:

0.755

TwinsUK

AF:

0.717

AC:

2659

ALSPAC

AF:

0.703

AC:

2711

ESP6500AA

AF:

0.878

AC:

3864

ESP6500EA

AF:

0.687

AC:

5911

ExAC

AF:

0.728

AC:

88427

Asia WGS

AF:

0.849

AC:

2954

AN:

3478

EpiCase

AF:

0.699

EpiControl

AF:

0.694

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 09, 2018	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Megalencephalic leukoencephalopathy with subcortical cysts 2A

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 10, 2021

- -

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

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 10, 2021

- -

Megalencephalic leukoencephalopathy with subcortical cysts

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

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

0.050

BayesDel_addAF

Benign

-0.87

BayesDel_noAF

Benign

-0.88

CADD

Benign

DANN

Benign

0.82

DEOGEN2

Benign

0.014

Eigen

Benign

-0.85

Eigen_PC

Benign

-0.64

FATHMM_MKL

Benign

0.38

LIST_S2

Benign

0.13

MetaRNN

Benign

0.0000011

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-0.47

MutationTaster

Benign

1.0

PrimateAI

Benign

0.43

PROVEAN

Benign

-0.24

REVEL

Benign

0.052

Sift

Benign

0.83

Sift4G

Benign

0.75

Polyphen

0.0

Vest4

0.029

MPC

0.31

ClinPred

0.00073

GERP RS

2.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.052

gMVP

0.29

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over