chr11-124919932-A-T
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1
The NM_001037558.4(HEPN1):c.182A>T(p.His61Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0857 in 1,613,728 control chromosomes in the GnomAD database, including 6,429 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.074 ( 435 hom., cov: 31)
Exomes 𝑓: 0.087 ( 5994 hom. )
Consequence
HEPN1
NM_001037558.4 missense
NM_001037558.4 missense
Scores
16
Clinical Significance
Conservation
PhyloP100: 0.0890
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]
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.0018495321).
BP6
?
Variant 11-124919932-A-T is Benign according to our data. Variant chr11-124919932-A-T is described in ClinVar as [Benign]. Clinvar id is 303297.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
?
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0943 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HEPN1 | NM_001037558.4 | c.182A>T | p.His61Leu | missense_variant | 1/1 | ENST00000408930.7 | |
HEPACAM | NM_152722.5 | c.*1206T>A | 3_prime_UTR_variant | 7/7 | ENST00000298251.5 | ||
LOC107984406 | XR_001748429.3 | n.335-23468A>T | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HEPN1 | ENST00000408930.7 | c.182A>T | p.His61Leu | missense_variant | 1/1 | NM_001037558.4 | P1 | ||
HEPACAM | ENST00000298251.5 | c.*1206T>A | 3_prime_UTR_variant | 7/7 | 1 | NM_152722.5 | P1 | ||
HEPACAM | ENST00000703807.1 | c.*1206T>A | 3_prime_UTR_variant | 7/7 |
Frequencies
GnomAD3 genomes ? AF: 0.0739 AC: 11235AN: 151946Hom.: 437 Cov.: 31
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GnomAD3 exomes AF: 0.0685 AC: 16922AN: 247136Hom.: 692 AF XY: 0.0707 AC XY: 9491AN XY: 134300
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GnomAD4 exome AF: 0.0870 AC: 127137AN: 1461664Hom.: 5994 Cov.: 34 AF XY: 0.0870 AC XY: 63255AN XY: 727134
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GnomAD4 genome ? AF: 0.0739 AC: 11232AN: 152064Hom.: 435 Cov.: 31 AF XY: 0.0711 AC XY: 5289AN XY: 74336
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Megalencephalic leukoencephalopathy with subcortical cysts Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 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:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationTaster
Benign
P;P
PrimateAI
Benign
T
PROVEAN
Benign
N
REVEL
Benign
Sift4G
Benign
T
Polyphen
B
Vest4
MPC
ClinPred
T
GERP RS
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gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at