chr7-81729637-C-T
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Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_ModerateBP6BP7BS2
The NM_000601.6(HGF):c.1008G>A(p.Glu336=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00278 in 1,613,782 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.0019 ( 1 hom., cov: 32)
Exomes 𝑓: 0.0029 ( 8 hom. )
Consequence
HGF
NM_000601.6 synonymous
NM_000601.6 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.509
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.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.36).
BP6
Variant 7-81729637-C-T is Benign according to our data. Variant chr7-81729637-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 43606.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=3, Uncertain_significance=1, Benign=2}. Variant chr7-81729637-C-T is described in Lovd as [Benign]. Variant chr7-81729637-C-T is described in Lovd as [Likely_benign].
BP7
Synonymous conserved (PhyloP=-0.509 with no splicing effect.
BS2
High Homozygotes in GnomAdExome4 at 8 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HGF | NM_000601.6 | c.1008G>A | p.Glu336= | synonymous_variant | 8/18 | ENST00000222390.11 | |
HGF | NM_001010932.3 | c.993G>A | p.Glu331= | synonymous_variant | 8/18 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HGF | ENST00000222390.11 | c.1008G>A | p.Glu336= | synonymous_variant | 8/18 | 1 | NM_000601.6 | P4 | |
HGF | ENST00000457544.7 | c.993G>A | p.Glu331= | synonymous_variant | 8/18 | 1 | A1 |
Frequencies
GnomAD3 genomes AF: 0.00192 AC: 292AN: 152094Hom.: 1 Cov.: 32
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GnomAD3 exomes AF: 0.00170 AC: 428AN: 251444Hom.: 1 AF XY: 0.00155 AC XY: 210AN XY: 135896
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GnomAD4 exome AF: 0.00286 AC: 4187AN: 1461570Hom.: 8 Cov.: 31 AF XY: 0.00278 AC XY: 2018AN XY: 727112
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GnomAD4 genome AF: 0.00192 AC: 292AN: 152212Hom.: 1 Cov.: 32 AF XY: 0.00177 AC XY: 132AN XY: 74430
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:6
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not provided Uncertain:1Benign:3
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Aug 01, 2023 | HGF: BP4, BP7 - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Mar 09, 2017 | - - |
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Dec 25, 2023 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 27, 2020 | - - |
not specified Benign:2
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Apr 30, 2012 | Glu336Glu in Exon 08 of HGF: This variant is not expected to have clinical signi ficance because it does not alter an amino acid residue, is not located within t he splice consensus sequence, and has been identified in 0.3% (24/7020) of Europ ean American chromosomes from a broad population by the NHLBI Exome Sequencing P roject (http://evs.gs.washington.edu/EVS; dbSNP rs148714837). - |
Autosomal recessive nonsyndromic hearing loss 39 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | Jun 28, 2017 | - - |
Computational scores
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BayesDel_noAF
Benign
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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