rs116102273

chr11-124921418-T-Cchr11-124921418-T-G

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.971A>G(p.Asn324Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0408 in 1,270,318 control chromosomes in the GnomAD database, including 1,303 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.055 (293 hom., cov: 32)
  • Exomes 𝑓: 0.039 (1010 hom.)
• Consequence: HEPACAM NM_152722.5 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.624

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 (MetaRNN=0.0013171732).
• BP6: Variant 11-124921418-T-C is Benign according to our data. Variant chr11-124921418-T-C is described in ClinVar as [Benign]. Clinvar id is 262683.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0905 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HEPACAM	NM_152722.5	c.971A>G	p.Asn324Ser	missense_variant	7/7	ENST00000298251.5
LOC107984406	XR_001748429.3	n.335-21982T>C		intron_variant, non_coding_transcript_variant
HEPACAM	NM_001411043.1	c.1127A>G	p.Asn376Ser	missense_variant	7/7
HEPACAM	XM_005271449.3	c.968A>G	p.Asn323Ser	missense_variant	7/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HEPACAM	ENST00000298251.5	c.971A>G	p.Asn324Ser	missense_variant	7/7	1	NM_152722.5	P1
HEPACAM	ENST00000703807.1	c.1127A>G	p.Asn376Ser	missense_variant	7/7

Frequencies

GnomAD3 genomes AF: 0.0549 AC: 8345 AN: 151884 Hom.: 291 Cov.: 32

Gnomad AFR AF: 0.0928

Gnomad AMI AF: 0.0286

Gnomad AMR AF: 0.0502

Gnomad ASJ AF: 0.0580

Gnomad EAS AF: 0.0683

Gnomad SAS AF: 0.0544

Gnomad FIN AF: 0.0231

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0371

Gnomad OTH AF: 0.0584

GnomAD3 exomes AF: 0.0217 AC: 299 AN: 13808 Hom.: 9 AF XY: 0.0221 AC XY: 179 AN XY: 8088

Gnomad AFR exome AF: 0.0561

Gnomad AMR exome AF: 0.0156

Gnomad ASJ exome AF: 0.0390

Gnomad EAS exome AF: 0.0464

Gnomad SAS exome AF: 0.0222

Gnomad FIN exome AF: 0.0150

Gnomad NFE exome AF: 0.0175

Gnomad OTH exome AF: 0.00585

GnomAD4 exome AF: 0.0389 AC: 43470 AN: 1118320 Hom.: 1010 Cov.: 34 AF XY: 0.0387 AC XY: 20604 AN XY: 532976

Gnomad4 AFR exome AF: 0.0898

Gnomad4 AMR exome AF: 0.0362

Gnomad4 ASJ exome AF: 0.0557

Gnomad4 EAS exome AF: 0.0668

Gnomad4 SAS exome AF: 0.0435

Gnomad4 FIN exome AF: 0.0208

Gnomad4 NFE exome AF: 0.0365

Gnomad4 OTH exome AF: 0.0461

GnomAD4 genome AF: 0.0550 AC: 8360 AN: 151998 Hom.: 293 Cov.: 32 AF XY: 0.0553 AC XY: 4108 AN XY: 74304

Gnomad4 AFR AF: 0.0930

Gnomad4 AMR AF: 0.0502

Gnomad4 ASJ AF: 0.0580

Gnomad4 EAS AF: 0.0681

Gnomad4 SAS AF: 0.0540

Gnomad4 FIN AF: 0.0231

Gnomad4 NFE AF: 0.0371

Gnomad4 OTH AF: 0.0578

Alfa AF: 0.0422 Hom.: 113

Bravo AF: 0.0578

TwinsUK AF: 0.0343 AC: 127

ALSPAC AF: 0.0324 AC: 125

ESP6500AA AF: 0.0489 AC: 157

ESP6500EA AF: 0.0226 AC: 154

ExAC AF: 0.0153 AC: 1555

Asia WGS AF: 0.0770 AC: 266 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 30, 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 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
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.72	T
BayesDel_noAF	Benign	-0.73
Cadd	Benign	8.8
Dann	Benign	0.47
DEOGEN2	Benign	0.0043	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.49	N
LIST_S2	Benign	0.59	T
MetaRNN	Benign	0.0013	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.34	N
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.39	T
PROVEAN	Benign	0.20	N
REVEL	Benign	0.035
Sift	Benign	0.22	T
Sift4G	Benign	0.71	T
Polyphen		0.0	B
Vest4		0.020
MPC		1.3
ClinPred		0.0083	T
GERP RS		-1.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.043
gMVP		0.13

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: rs116102273; hg19: chr11-124791314; COSMIC: COSV53430516; COSMIC: COSV53430516;