rs10790716

Positions:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_152722.5(HEPACAM):c.618C>T(p.Arg206=) 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:7

Conservation

PhyloP100: -6.89

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 -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
HEPACAM	NM_152722.5 linkuse as main transcript	c.618C>T	p.Arg206=	synonymous_variant	3/7	ENST00000298251.5
LOC107984406	XR_001748429.3 linkuse as main transcript	n.335-19580G>A		intron_variant, non_coding_transcript_variant
HEPACAM	NM_001411043.1 linkuse as main transcript	c.618C>T	p.Arg206=	synonymous_variant	3/7
HEPACAM	XM_005271449.3 linkuse as main transcript	c.618C>T	p.Arg206=	synonymous_variant	3/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HEPACAM	ENST00000298251.5 linkuse as main transcript	c.618C>T	p.Arg206=	synonymous_variant	3/7	1	NM_152722.5	P1	Q14CZ8-1
HEPACAM	ENST00000703807.1 linkuse as main transcript	c.618C>T	p.Arg206=	synonymous_variant	3/7
HEPACAM	ENST00000526273.1 linkuse as main transcript	n.390C>T		non_coding_transcript_exon_variant	2/2	2

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

GnomAD3 exomes

AF:

0.198

AC:

49823

AN:

251344

Hom.:

5742

AF XY:

0.201

AC XY:

27271

AN XY:

135854

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 SAS exome

AF:

0.120

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

Gnomad4 AFR exome

AF:

0.115

Gnomad4 AMR exome

AF:

0.125

Gnomad4 ASJ exome

AF:

0.142

Gnomad4 EAS exome

AF:

0.0968

Gnomad4 SAS exome

AF:

0.118

Gnomad4 FIN exome

AF:

0.238

Gnomad4 NFE exome

AF:

0.278

Gnomad4 OTH exome

AF:

0.231

GnomAD4 genome

AF:

0.204

AC:

31061

AN:

152196

Hom.:

3579

Cov.:

AF XY:

0.198

AC XY:

14736

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.128

Gnomad4 AMR

AF:

0.157

Gnomad4 ASJ

AF:

0.138

Gnomad4 EAS

AF:

0.0772

Gnomad4 SAS

AF:

0.113

Gnomad4 FIN

AF:

0.233

Gnomad4 NFE

AF:

0.275

Gnomad4 OTH

AF:

0.211

Alfa

AF:

0.244

Hom.:

6431

Bravo

AF:

0.195

EpiCase

AF:

0.265

EpiControl

AF:

0.257

ClinVar

Significance: Benign

Submissions summary: Benign:7

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 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

BayesDel_noAF

Benign

-0.77

CADD

Benign

0.23

DANN

Benign

0.86

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

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