rs886047920

Variant names:

• chr11-124920149-C-A
• rs886047920
• NM_152722.5:c.*989G>T

Your query was ambiguous. Multiple possible variants found:

• chr11-124920149-C-A
• chr11-124920149-C-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.*989G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000163 in 1,058,408 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 0.00058 (0 hom., cov: 30)
  • Exomes 𝑓: 0.000093 (0 hom.)
• Consequence: HEPACAM NM_152722.5 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.83
• 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=-0.89).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.000585 (89/152140) while in subpopulation AFR AF = 0.00205 (85/41414). AF 95% confidence interval is 0.0017. There are 0 homozygotes in GnomAd4. There are 47 alleles in the male GnomAd4 subpopulation. Median coverage is 30. 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.*989G>T		3_prime_UTR	Exon 7 of 7	NP_689935.2	Q14CZ8-1
	HEPN1	NM_001037558.4	MANE Select	c.*132C>A		3_prime_UTR	Exon 1 of 1	NP_001032647.2	Q6WQI6
	HEPACAM	NM_001411043.1		c.*989G>T		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.*989G>T		3_prime_UTR	Exon 7 of 7	ENSP00000298251.4	Q14CZ8-1
	HEPN1	ENST00000408930.7	TSL:6 MANE Select	c.*132C>A		3_prime_UTR	Exon 1 of 1	ENSP00000386143.4	Q6WQI6
	HEPACAM	ENST00000703807.1		c.*989G>T		3_prime_UTR	Exon 7 of 7	ENSP00000515485.1	A0A994J4I1

Frequencies

GnomAD3 genomes AF: 0.000585 AC: 89 AN: 152140 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.00205

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000927 AC: 84 AN: 906268 Hom.: 0 Cov.: 12 AF XY: 0.0000875 AC XY: 40 AN XY: 457040

African (AFR) AF: 0.00220 AC: 47 AN: 21356

American (AMR) AF: 0.000119 AC: 3 AN: 25180

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16972

East Asian (EAS) AF: 0.000578 AC: 21 AN: 36354

South Asian (SAS) AF: 0.00 AC: 0 AN: 58290

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47844

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2926

European-Non Finnish (NFE) AF: 0.00000914 AC: 6 AN: 656214

Other (OTH) AF: 0.000170 AC: 7 AN: 41132

GnomAD4 genome AF: 0.000585 AC: 89 AN: 152140 Hom.: 0 Cov.: 30 AF XY: 0.000632 AC XY: 47 AN XY: 74318

African (AFR) AF: 0.00205 AC: 85 AN: 41414

American (AMR) AF: 0.000196 AC: 3 AN: 15290

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

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68020

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.000296 Hom.: 0

Bravo AF: 0.000812

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	-0.89
CADD	Benign	0.14
DANN	Benign	0.28
PhyloP100		-2.8

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: rs886047920; hg19: chr11-124790045;