11-124922731-G-A

Position:

chr11-124922731-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_152722.5(HEPACAM):c.877+14C>T variant causes a intron 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_152722.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.109

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 -20 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 id is 262682.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
HEPACAM	NM_152722.5 linkuse as main transcript	c.877+14C>T		intron_variant		ENST00000298251.5
LOC107984406	XR_001748429.3 linkuse as main transcript	n.335-20669G>A		intron_variant, non_coding_transcript_variant
HEPACAM	NM_001411043.1 linkuse as main transcript	c.891C>T	p.Ala297=	synonymous_variant	5/7
HEPACAM	XM_005271449.3 linkuse as main transcript	c.877+14C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HEPACAM	ENST00000298251.5 linkuse as main transcript	c.877+14C>T		intron_variant		1	NM_152722.5	P1	Q14CZ8-1
HEPACAM	ENST00000703807.1 linkuse as main transcript	c.891C>T	p.Ala297=	synonymous_variant	5/7

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

GnomAD3 exomes

AF:

0.102

AC:

25772

AN:

251490

Hom.:

1731

AF XY:

0.0992

AC XY:

13490

AN XY:

135920

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 SAS exome

AF:

0.0784

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

Gnomad4 AFR exome

AF:

0.299

Gnomad4 AMR exome

AF:

0.0663

Gnomad4 ASJ exome

AF:

0.115

Gnomad4 EAS exome

AF:

0.0709

Gnomad4 SAS exome

AF:

0.0790

Gnomad4 FIN exome

AF:

0.117

Gnomad4 NFE exome

AF:

0.0916

Gnomad4 OTH exome

AF:

0.107

GnomAD4 genome

AF:

0.147

AC:

22405

AN:

152216

Hom.:

2292

Cov.:

AF XY:

0.145

AC XY:

10824

AN XY:

74430

show subpopulations

Gnomad4 AFR

AF:

0.286

Gnomad4 AMR

AF:

0.0920

Gnomad4 ASJ

AF:

0.116

Gnomad4 EAS

AF:

0.0523

Gnomad4 SAS

AF:

0.0810

Gnomad4 FIN

AF:

0.126

Gnomad4 NFE

AF:

0.0916

Gnomad4 OTH

AF:

0.127

Alfa

AF:

0.105

Hom.:

1053

Bravo

AF:

0.154

Asia WGS

AF:

0.0750

AC:

262

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

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 21, 2018	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

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

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Benign

0.76

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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