rs142045938
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Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6BP7
The NM_000601.6(HGF):āc.471A>Gā(p.Pro157=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000143 in 1,542,856 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 Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: š 0.00014 ( 0 hom., cov: 32)
Exomes š: 0.00014 ( 0 hom. )
Consequence
HGF
NM_000601.6 synonymous
NM_000601.6 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.672
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 Likely_benign. Variant got -4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.51).
BP6
Variant 7-81757200-T-C is Benign according to our data. Variant chr7-81757200-T-C is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 227427.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=2, Uncertain_significance=1}.
BP7
Synonymous conserved (PhyloP=0.672 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HGF | NM_000601.6 | c.471A>G | p.Pro157= | synonymous_variant | 4/18 | ENST00000222390.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HGF | ENST00000222390.11 | c.471A>G | p.Pro157= | synonymous_variant | 4/18 | 1 | NM_000601.6 | P4 |
Frequencies
GnomAD3 genomes AF: 0.000138 AC: 21AN: 152192Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000835 AC: 21AN: 251388Hom.: 0 AF XY: 0.000103 AC XY: 14AN XY: 135850
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GnomAD4 exome AF: 0.000144 AC: 200AN: 1390664Hom.: 0 Cov.: 24 AF XY: 0.000141 AC XY: 98AN XY: 696632
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GnomAD4 genome AF: 0.000138 AC: 21AN: 152192Hom.: 0 Cov.: 32 AF XY: 0.0000807 AC XY: 6AN XY: 74358
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:2
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Nonsyndromic Hearing Loss, Mixed Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Apr 30, 2012 | Pro157Pro in Exon 04 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 2/7020 European America n chromosomes from a broad population by the NHLBI Exome Sequencing Project (htt p://evs.gs.washington.edu/EVS; dbSNP rs142045938). - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 02, 2019 | - - |
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