7-81743342-C-T
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Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 2P and 10B. PM2BP4_ModerateBP6_Very_Strong
The NM_000601.6(HGF):c.865+11G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000567 in 1,482,194 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 Likely benign (★★).
Frequency
Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000058 ( 0 hom. )
Consequence
HGF
NM_000601.6 intron
NM_000601.6 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 2.42
Genes affected
HGF (HGNC:4893): (hepatocyte growth factor) This gene encodes a protein that binds to the hepatocyte growth factor receptor to regulate cell growth, cell motility and morphogenesis in numerous cell and tissue types. Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein that is proteolytically processed to generate alpha and beta chains, which form the mature heterodimer. This protein is secreted by mesenchymal cells and acts as a multi-functional cytokine on cells of mainly epithelial origin. This protein also plays a role in angiogenesis, tumorogenesis, and tissue regeneration. Although the encoded protein is a member of the peptidase S1 family of serine proteases, it lacks peptidase activity. Mutations in this gene are associated with nonsyndromic hearing loss. [provided by RefSeq, Nov 2015]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -8 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.2).
BP6
Variant 7-81743342-C-T is Benign according to our data. Variant chr7-81743342-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 517565.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
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HGF | ENST00000222390.11 | c.865+11G>A | intron_variant | 1 | NM_000601.6 | ENSP00000222390.5 | ||||
HGF | ENST00000457544.7 | c.850+11G>A | intron_variant | 1 | ENSP00000391238.2 | |||||
HGF | ENST00000444829.7 | c.865+11G>A | intron_variant | 1 | ENSP00000389854.2 | |||||
HGF | ENST00000453411.6 | c.850+11G>A | intron_variant | 1 | ENSP00000408270.1 |
Frequencies
GnomAD3 genomes AF: 0.0000460 AC: 7AN: 152162Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000517 AC: 13AN: 251426Hom.: 0 AF XY: 0.0000515 AC XY: 7AN XY: 135878
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GnomAD4 exome AF: 0.0000579 AC: 77AN: 1330032Hom.: 0 Cov.: 20 AF XY: 0.0000613 AC XY: 41AN XY: 669200
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GnomAD4 genome AF: 0.0000460 AC: 7AN: 152162Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3AN XY: 74330
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Nov 22, 2017 | c.865+11G>A in intron 7 of HGF: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue and is not located wi thin the splice consensus sequence. It has been identified in 0.01% (15/126668) of European chromosomes by the Genome Aggregation Database (gnomAD, http://gnomA D.broadinstitute.org; dbSNP rs761252474). - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Nov 23, 2024 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at