chr11-124921088-G-C

Position:

• chr11-124921088-G-C

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.*50C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0166 in 1,511,120 control chromosomes in the GnomAD database, including 376 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.015 (65 hom., cov: 32)
  • Exomes 𝑓: 0.017 (311 hom.)
• Consequence: HEPACAM NM_152722.5 3_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -4.25

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=-0.91).
• BP6: Variant 11-124921088-G-C is Benign according to our data. Variant chr11-124921088-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 262676.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0581 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HEPACAM	NM_152722.5	c.*50C>G		3_prime_UTR_variant	7/7	ENST00000298251.5	NP_689935.2
HEPACAM	NM_001411043.1	c.*50C>G		3_prime_UTR_variant	7/7		NP_001397972.1
HEPACAM	XM_005271449.3	c.*50C>G		3_prime_UTR_variant	7/7		XP_005271506.1
LOC107984406	XR_001748429.3	n.335-22312G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HEPACAM	ENST00000298251	c.*50C>G		3_prime_UTR_variant	7/7	1	NM_152722.5	ENSP00000298251.4
HEPACAM	ENST00000703807	c.*50C>G		3_prime_UTR_variant	7/7			ENSP00000515485.1

Frequencies

GnomAD3 genomes AF: 0.0146 AC: 2214 AN: 152138 Hom.: 65 Cov.: 32

Gnomad AFR AF: 0.00338

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0611

Gnomad ASJ AF: 0.0110

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.00292

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0153

Gnomad OTH AF: 0.0115

GnomAD3 exomes AF: 0.0222 AC: 2513 AN: 113286 Hom.: 78 AF XY: 0.0184 AC XY: 1150 AN XY: 62628

Gnomad AFR exome AF: 0.00379

Gnomad AMR exome AF: 0.0742

Gnomad ASJ exome AF: 0.0113

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00169

Gnomad FIN exome AF: 0.00281

Gnomad NFE exome AF: 0.0159

Gnomad OTH exome AF: 0.0172

GnomAD4 exome AF: 0.0168 AC: 22853 AN: 1358866 Hom.: 311 Cov.: 34 AF XY: 0.0162 AC XY: 10847 AN XY: 669694

Gnomad4 AFR exome AF: 0.00293

Gnomad4 AMR exome AF: 0.0785

Gnomad4 ASJ exome AF: 0.00867

Gnomad4 EAS exome AF: 0.0000294

Gnomad4 SAS exome AF: 0.00184

Gnomad4 FIN exome AF: 0.00414

Gnomad4 NFE exome AF: 0.0176

Gnomad4 OTH exome AF: 0.0154

GnomAD4 genome AF: 0.0146 AC: 2218 AN: 152254 Hom.: 65 Cov.: 32 AF XY: 0.0147 AC XY: 1095 AN XY: 74440

Gnomad4 AFR AF: 0.00337

Gnomad4 AMR AF: 0.0613

Gnomad4 ASJ AF: 0.0110

Gnomad4 EAS AF: 0.000387

Gnomad4 SAS AF: 0.00124

Gnomad4 FIN AF: 0.00292

Gnomad4 NFE AF: 0.0153

Gnomad4 OTH AF: 0.0113

Alfa AF: 0.0133 Hom.: 8

Bravo AF: 0.0180

Asia WGS AF: 0.00289 AC: 10 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 03, 2018	- -

not specified Benign:1

Likely 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	-0.91
CADD	Benign	0.90
DANN	Benign	0.68

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: rs192160991; hg19: chr11-124790984;