rs11826299

chr11-124922731-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.109

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 -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	UniProt
HEPACAM	NM_152722.5	c.877+14C>T		intron_variant		ENST00000298251.5
LOC107984406	XR_001748429.3	n.335-20669G>A		intron_variant, non_coding_transcript_variant
HEPACAM	NM_001411043.1	c.891C>T	p.Ala297=	synonymous_variant	5/7
HEPACAM	XM_005271449.3	c.877+14C>T		intron_variant

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.147 AC: 22393 AN: 152098 Hom.: 2292 Cov.: 32

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

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.: 34 AF XY: 0.0956 AC XY: 69494 AN XY: 727218

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.: 32 AF XY: 0.145 AC XY: 10824 AN XY: 74430

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:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 21, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 29, 2024	- -

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	15
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

Other links and lift over

dbSNP: rs11826299; hg19: chr11-124792627; COSMIC: COSV53429899; COSMIC: COSV53429899;