rs537876767

Variant names:

• chr11-124920105-T-C
• rs537876767
• NM_152722.5:c.*1033A>G

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Strong BS1_Supporting

The NM_152722.5(HEPACAM):​c.*1033A>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 0.0000745 in 1,422,748 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 30)
  • Exomes 𝑓: 0.000079 (0 hom.)
• Consequence: HEPACAM NM_152722.5 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.999
• Publications: 0 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]

HEPN1 (HGNC:34400): (hepatocellular carcinoma, down-regulated 1) This gene is expressed predominantly in the liver. Transient transfection studies show the expression of this gene significantly inhibits cell growth, suggesting a role for this gene in apoptosis. Expression of this gene is down-regulated or lost in hepatocellular carcinomas (HCC), suggesting that loss of this gene is involved in carcinogenesis of hepatocytes (PMID:12971969). This gene maps to the 3'-noncoding region of the HEPACAM gene (GeneID:220296) on the antisense strand. [provided by RefSeq, Aug 2020]

ENSG00000254943 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BS1: Variant frequency is greater than expected in population eas. GnomAdExome4 allele frequency = 0.0000795 (101/1270546) while in subpopulation EAS AF = 0.00218 (84/38498). AF 95% confidence interval is 0.00181. There are 0 homozygotes in GnomAdExome4. There are 54 alleles in the male GnomAdExome4 subpopulation. Median coverage is 19. This position passed quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HEPACAM	NM_152722.5	MANE Select	c.*1033A>G		3_prime_UTR	Exon 7 of 7	NP_689935.2	Q14CZ8-1
	HEPN1	NM_001037558.4	MANE Select	c.*88T>C		3_prime_UTR	Exon 1 of 1	NP_001032647.2	Q6WQI6
	HEPACAM	NM_001411043.1		c.*1033A>G		3_prime_UTR	Exon 7 of 7	NP_001397972.1	A0A994J4I1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HEPACAM	ENST00000298251.5	TSL:1 MANE Select	c.*1033A>G		3_prime_UTR	Exon 7 of 7	ENSP00000298251.4	Q14CZ8-1
	HEPN1	ENST00000408930.7	TSL:6 MANE Select	c.*88T>C		3_prime_UTR	Exon 1 of 1	ENSP00000386143.4	Q6WQI6
	HEPACAM	ENST00000703807.1		c.*1033A>G		3_prime_UTR	Exon 7 of 7	ENSP00000515485.1	A0A994J4I1

Frequencies

GnomAD3 genomes AF: 0.0000329 AC: 5 AN: 152084 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000580

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.000478

GnomAD4 exome AF: 0.0000795 AC: 101 AN: 1270546 Hom.: 0 Cov.: 19 AF XY: 0.0000858 AC XY: 54 AN XY: 629532

African (AFR) AF: 0.00 AC: 0 AN: 28542

American (AMR) AF: 0.00 AC: 0 AN: 33322

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20412

East Asian (EAS) AF: 0.00218 AC: 84 AN: 38498

South Asian (SAS) AF: 0.0000143 AC: 1 AN: 69810

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49998

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3560

European-Non Finnish (NFE) AF: 0.0000123 AC: 12 AN: 973436

Other (OTH) AF: 0.0000755 AC: 4 AN: 52968

GnomAD4 genome AF: 0.0000329 AC: 5 AN: 152202 Hom.: 0 Cov.: 30 AF XY: 0.0000269 AC XY: 2 AN XY: 74432

African (AFR) AF: 0.00 AC: 0 AN: 41520

American (AMR) AF: 0.00 AC: 0 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000582 AC: 3 AN: 5158

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67988

Other (OTH) AF: 0.000473 AC: 1 AN: 2112

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000302

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Megalencephalic leukoencephalopathy with subcortical cysts (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.20
DANN	Benign	0.75
PhyloP100		-1.0
Mutation Taster		=100/0	polymorphism

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: rs537876767; hg19: chr11-124790001;