rs112686308

chr11-124924792-C-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_152722.5(HEPACAM):c.363G>A(p.Glu121=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0396 in 1,614,042 control chromosomes in the GnomAD database, including 1,480 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.028 (72 hom., cov: 32)
  • Exomes 𝑓: 0.041 (1408 hom.)
• Consequence: HEPACAM NM_152722.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.0110

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]

LOC107984406 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BP6: Variant 11-124924792-C-T is Benign according to our data. Variant chr11-124924792-C-T is described in ClinVar as [Benign]. Clinvar id is 262678.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.011 with no splicing effect.
• BA1: GnomAdExome4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.051 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HEPACAM	NM_152722.5	c.363G>A	p.Glu121=	synonymous_variant	2/7	ENST00000298251.5
LOC107984406	XR_001748429.3	n.335-18608C>T		intron_variant, non_coding_transcript_variant
HEPACAM	NM_001411043.1	c.363G>A	p.Glu121=	synonymous_variant	2/7
HEPACAM	XM_005271449.3	c.363G>A	p.Glu121=	synonymous_variant	2/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HEPACAM	ENST00000298251.5	c.363G>A	p.Glu121=	synonymous_variant	2/7	1	NM_152722.5	P1
HEPACAM	ENST00000703807.1	c.363G>A	p.Glu121=	synonymous_variant	2/7
HEPACAM	ENST00000526273.1	n.135G>A		non_coding_transcript_exon_variant	1/2	2
HEPACAM	ENST00000528971.1	n.769G>A		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes AF: 0.0280 AC: 4257 AN: 152080 Hom.: 73 Cov.: 32

Gnomad AFR AF: 0.00821

Gnomad AMI AF: 0.0406

Gnomad AMR AF: 0.0214

Gnomad ASJ AF: 0.0135

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.0465

Gnomad FIN AF: 0.0173

Gnomad MID AF: 0.0318

Gnomad NFE AF: 0.0447

Gnomad OTH AF: 0.0206

GnomAD3 exomes AF: 0.0302 AC: 7594 AN: 251432 Hom.: 172 AF XY: 0.0331 AC XY: 4503 AN XY: 135898

Gnomad AFR exome AF: 0.00714

Gnomad AMR exome AF: 0.0115

Gnomad ASJ exome AF: 0.0147

Gnomad EAS exome AF: 0.000326

Gnomad SAS exome AF: 0.0520

Gnomad FIN exome AF: 0.0205

Gnomad NFE exome AF: 0.0415

Gnomad OTH exome AF: 0.0282

GnomAD4 exome AF: 0.0409 AC: 59724 AN: 1461844 Hom.: 1408 Cov.: 31 AF XY: 0.0415 AC XY: 30216 AN XY: 727228

Gnomad4 AFR exome AF: 0.00570

Gnomad4 AMR exome AF: 0.0127

Gnomad4 ASJ exome AF: 0.0143

Gnomad4 EAS exome AF: 0.000126

Gnomad4 SAS exome AF: 0.0523

Gnomad4 FIN exome AF: 0.0204

Gnomad4 NFE exome AF: 0.0453

Gnomad4 OTH exome AF: 0.0409

GnomAD4 genome AF: 0.0279 AC: 4253 AN: 152198 Hom.: 72 Cov.: 32 AF XY: 0.0274 AC XY: 2043 AN XY: 74428

Gnomad4 AFR AF: 0.00819

Gnomad4 AMR AF: 0.0214

Gnomad4 ASJ AF: 0.0135

Gnomad4 EAS AF: 0.000580

Gnomad4 SAS AF: 0.0465

Gnomad4 FIN AF: 0.0173

Gnomad4 NFE AF: 0.0447

Gnomad4 OTH AF: 0.0204

Alfa AF: 0.0359 Hom.: 43

Bravo AF: 0.0260

Asia WGS AF: 0.0180 AC: 63 AN: 3478

EpiCase AF: 0.0457

EpiControl AF: 0.0413

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 29, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 03, 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
BayesDel_noAF	Benign	-0.39
Cadd	Benign	8.4
Dann	Benign	0.87

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

Other links and lift over

dbSNP: rs112686308; hg19: chr11-124794688; COSMIC: COSV53428590; COSMIC: COSV53428590;