Variant 11-124919846-AAGG-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 1P and 0B. PM4_Supporting

The NM_001037558.4(HEPN1):c.103_105del(p.Arg35del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00133 in 1,614,136 control chromosomes in the GnomAD database, including 2 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00081 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0014 ( 2 hom. )

Consequence

HEPN1
NM_001037558.4 inframe_deletion

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.31

Variant links:

Genes affected

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]

HEPN1 links:

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]

HEPACAM links:

LOC107984406 (HGNC:):

LOC107984406 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM4

Nonframeshift variant in NON repetitive region in NM_001037558.4. Strenght limited to Supporting due to length of the change: 1aa.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
HEPN1	NM_001037558.4 linkuse as main transcript	c.103_105del	p.Arg35del	inframe_deletion	1/1	ENST00000408930.7
HEPACAM	NM_152722.5 linkuse as main transcript	c.1289_1291del		3_prime_UTR_variant	7/7	ENST00000298251.5
LOC107984406	XR_001748429.3 linkuse as main transcript	n.335-23547_335-23545del		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HEPN1	ENST00000408930.7 linkuse as main transcript	c.103_105del	p.Arg35del	inframe_deletion	1/1		NM_001037558.4	P1
HEPACAM	ENST00000298251.5 linkuse as main transcript	c.1289_1291del		3_prime_UTR_variant	7/7	1	NM_152722.5	P1	Q14CZ8-1
HEPACAM	ENST00000703807.1 linkuse as main transcript	c.1289_1291del		3_prime_UTR_variant	7/7

Frequencies

GnomAD3 genomes

AF:

0.000815

AC:

124

AN:

152174

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00159

Gnomad OTH

AF:

0.000955

GnomAD3 exomes

AF:

0.000781

AC:

193

AN:

247122

Hom.:

AF XY:

0.000812

AC XY:

109

AN XY:

134292

show subpopulations

Gnomad AFR exome

AF:

0.000258

Gnomad AMR exome

AF:

0.000261

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000139

Gnomad NFE exome

AF:

0.00156

Gnomad OTH exome

AF:

0.000662

GnomAD4 exome

AF:

0.00138

AC:

2017

AN:

1461844

Hom.:

AF XY:

0.00130

AC XY:

949

AN XY:

727230

show subpopulations

Gnomad4 AFR exome

AF:

0.000179

Gnomad4 AMR exome

AF:

0.000268

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.0000936

Gnomad4 NFE exome

AF:

0.00172

Gnomad4 OTH exome

AF:

0.00137

GnomAD4 genome

AF:

0.000814

AC:

124

AN:

152292

Hom.:

Cov.:

AF XY:

0.000685

AC XY:

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.000241

Gnomad4 AMR

AF:

0.000261

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00159

Gnomad4 OTH

AF:

0.000945

Alfa

AF:

0.00127

Hom.:

Bravo

AF:

0.000816

EpiCase

AF:

0.00191

EpiControl

AF:

0.00130

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Megalencephalic leukoencephalopathy with subcortical cysts

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over