rs116102273

Positions:

Variant summary

Our verdict is Benign. Variant got -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. 14/20 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

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 (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 id 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/exons	MANE	Protein	UniProt
HEPACAM	NM_152722.5 linkuse as main transcript	c.971A>G	p.Asn324Ser	missense_variant	7/7	ENST00000298251.5	NP_689935.2	Q14CZ8-1
HEPACAM	NM_001411043.1 linkuse as main transcript	c.1127A>G	p.Asn376Ser	missense_variant	7/7		NP_001397972.1
HEPACAM	XM_005271449.3 linkuse as main transcript	c.968A>G	p.Asn323Ser	missense_variant	7/7		XP_005271506.1
LOC107984406	XR_001748429.3 linkuse as main transcript	n.335-21982T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HEPACAM	ENST00000298251.5 linkuse as main transcript	c.971A>G	p.Asn324Ser	missense_variant	7/7	1	NM_152722.5	ENSP00000298251.4		Q14CZ8-1
HEPACAM	ENST00000703807.1 linkuse as main transcript	c.1127A>G	p.Asn376Ser	missense_variant	7/7			ENSP00000515485.1		A0A994J4I1

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

GnomAD3 exomes

AF:

0.0217

AC:

299

AN:

13808

Hom.:

AF XY:

0.0221

AC XY:

179

AN XY:

8088

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 SAS exome

AF:

0.0222

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

Gnomad4 AFR exome

AF:

0.0898

Gnomad4 AMR exome

AF:

0.0362

Gnomad4 ASJ exome

AF:

0.0557

Gnomad4 EAS exome

AF:

0.0668

Gnomad4 SAS exome

AF:

0.0435

Gnomad4 FIN exome

AF:

0.0208

Gnomad4 NFE exome

AF:

0.0365

Gnomad4 OTH exome

AF:

0.0461

GnomAD4 genome

AF:

0.0550

AC:

8360

AN:

151998

Hom.:

293

Cov.:

AF XY:

0.0553

AC XY:

4108

AN XY:

74304

show subpopulations

Gnomad4 AFR

AF:

0.0930

Gnomad4 AMR

AF:

0.0502

Gnomad4 ASJ

AF:

0.0580

Gnomad4 EAS

AF:

0.0681

Gnomad4 SAS

AF:

0.0540

Gnomad4 FIN

AF:

0.0231

Gnomad4 NFE

AF:

0.0371

Gnomad4 OTH

AF:

0.0578

Alfa

AF:

0.0422

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

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 30, 2024	- -
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 12, 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

0.080

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.73

CADD

Benign

8.8

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

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

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