chr11-124922731-G-A

Variant names:

• chr11-124922731-G-A
• rs11826299
• NM_152722.5:c.877+14C>T

Variant summary

Our verdict is Benign. The variant received -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:5
• Conservation: PhyloP100: 0.109
• Publications: 7 publications found

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 Gene-Disease associations (from GenCC):

• megalencephalic leukoencephalopathy with subcortical cysts 2B, remitting, with or without intellectual disability

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, ClinGen, Labcorp Genetics (formerly Invitae)
• megalencephalic leukoencephalopathy with subcortical cysts 2A

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, ClinGen, Labcorp Genetics (formerly Invitae)
• macrocephaly-autism syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• megalencephalic leukoencephalopathy with subcortical cysts

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000254943 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152722.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HEPACAM	NM_152722.5	MANE Select	c.877+14C>T		intron	N/A	NP_689935.2
	HEPACAM	NM_001411043.1		c.891C>T	p.Ala297Ala	synonymous	Exon 5 of 7	NP_001397972.1
	HEPACAM	NM_001441320.1		c.877+14C>T		intron	N/A	NP_001428249.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HEPACAM	ENST00000298251.5	TSL:1 MANE Select	c.877+14C>T		intron	N/A	ENSP00000298251.4
	HEPACAM	ENST00000703807.1		c.891C>T	p.Ala297Ala	synonymous	Exon 5 of 7	ENSP00000515485.1
	ENSG00000254943	ENST00000524433.2	TSL:4	n.484-20669G>A		intron	N/A

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

GnomAD2 exomes AF: 0.102 AC: 25772 AN: 251490 AF XY: 0.0992

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 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

African (AFR) AF: 0.299 AC: 10009 AN: 33480

American (AMR) AF: 0.0663 AC: 2965 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.115 AC: 3005 AN: 26134

East Asian (EAS) AF: 0.0709 AC: 2815 AN: 39698

South Asian (SAS) AF: 0.0790 AC: 6813 AN: 86258

European-Finnish (FIN) AF: 0.117 AC: 6259 AN: 53414

Middle Eastern (MID) AF: 0.151 AC: 869 AN: 5768

European-Non Finnish (NFE) AF: 0.0916 AC: 101850 AN: 1111944

Other (OTH) AF: 0.107 AC: 6442 AN: 60394

GnomAD4 genome AF: 0.147 AC: 22405 AN: 152216 Hom.: 2292 Cov.: 32 AF XY: 0.145 AC XY: 10824 AN XY: 74430

African (AFR) AF: 0.286 AC: 11868 AN: 41492

American (AMR) AF: 0.0920 AC: 1407 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.116 AC: 403 AN: 3472

East Asian (EAS) AF: 0.0523 AC: 271 AN: 5186

South Asian (SAS) AF: 0.0810 AC: 391 AN: 4828

European-Finnish (FIN) AF: 0.126 AC: 1334 AN: 10604

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.0916 AC: 6231 AN: 68016

Other (OTH) AF: 0.127 AC: 269 AN: 2116

Alfa AF: 0.111 Hom.: 1582

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

Submissions by phenotype

not provided Benign:3

Jul 21, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

not specified Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Megalencephalic leukoencephalopathy with subcortical cysts Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	15
DANN	Benign	0.76
PhyloP100		0.11
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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