rs74570840

Positions:

• chr11-124924816-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.339G>A​(p.Gln113=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.028 in 1,614,120 control chromosomes in the GnomAD database, including 875 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.031 (87 hom., cov: 32)
  • Exomes 𝑓: 0.028 (788 hom.)
• Consequence: HEPACAM NM_152722.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 1.71

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=-0.42).
• BP6: Variant 11-124924816-C-T is Benign according to our data. Variant chr11-124924816-C-T is described in ClinVar as [Benign]. Clinvar id is 262677.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.71 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0737 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HEPACAM	NM_152722.5	c.339G>A	p.Gln113=	synonymous_variant	2/7	ENST00000298251.5
LOC107984406	XR_001748429.3	n.335-18584C>T		intron_variant, non_coding_transcript_variant
HEPACAM	NM_001411043.1	c.339G>A	p.Gln113=	synonymous_variant	2/7
HEPACAM	XM_005271449.3	c.339G>A	p.Gln113=	synonymous_variant	2/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HEPACAM	ENST00000298251.5	c.339G>A	p.Gln113=	synonymous_variant	2/7	1	NM_152722.5	P1
HEPACAM	ENST00000703807.1	c.339G>A	p.Gln113=	synonymous_variant	2/7
HEPACAM	ENST00000526273.1	n.111G>A		non_coding_transcript_exon_variant	1/2	2
HEPACAM	ENST00000528971.1	n.745G>A		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes AF: 0.0306 AC: 4659 AN: 152126 Hom.: 89 Cov.: 32

Gnomad AFR AF: 0.0420

Gnomad AMI AF: 0.0208

Gnomad AMR AF: 0.0185

Gnomad ASJ AF: 0.0608

Gnomad EAS AF: 0.0799

Gnomad SAS AF: 0.0621

Gnomad FIN AF: 0.00697

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0228

Gnomad OTH AF: 0.0287

GnomAD3 exomes AF: 0.0334 AC: 8388 AN: 251482 Hom.: 237 AF XY: 0.0347 AC XY: 4713 AN XY: 135918

Gnomad AFR exome AF: 0.0419

Gnomad AMR exome AF: 0.0175

Gnomad ASJ exome AF: 0.0608

Gnomad EAS exome AF: 0.0919

Gnomad SAS exome AF: 0.0569

Gnomad FIN exome AF: 0.00827

Gnomad NFE exome AF: 0.0238

Gnomad OTH exome AF: 0.0279

GnomAD4 exome AF: 0.0277 AC: 40472 AN: 1461876 Hom.: 788 Cov.: 32 AF XY: 0.0286 AC XY: 20834 AN XY: 727240

Gnomad4 AFR exome AF: 0.0443

Gnomad4 AMR exome AF: 0.0175

Gnomad4 ASJ exome AF: 0.0610

Gnomad4 EAS exome AF: 0.0826

Gnomad4 SAS exome AF: 0.0547

Gnomad4 FIN exome AF: 0.00874

Gnomad4 NFE exome AF: 0.0233

Gnomad4 OTH exome AF: 0.0321

GnomAD4 genome AF: 0.0306 AC: 4661 AN: 152244 Hom.: 87 Cov.: 32 AF XY: 0.0300 AC XY: 2235 AN XY: 74450

Gnomad4 AFR AF: 0.0420

Gnomad4 AMR AF: 0.0185

Gnomad4 ASJ AF: 0.0608

Gnomad4 EAS AF: 0.0801

Gnomad4 SAS AF: 0.0615

Gnomad4 FIN AF: 0.00697

Gnomad4 NFE AF: 0.0228

Gnomad4 OTH AF: 0.0284

Alfa AF: 0.0284 Hom.: 44

Bravo AF: 0.0327

Asia WGS AF: 0.0460 AC: 162 AN: 3478

EpiCase AF: 0.0220

EpiControl AF: 0.0241

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 25, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 31, 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	-0.42
CADD	Benign	7.7
DANN	Benign	0.87

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: rs74570840; hg19: chr11-124794712; COSMIC: COSV53429971; COSMIC: COSV53429971;