chr7-81702185-T-A
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Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_000601.6(HGF):c.*396A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00299 in 238,184 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0031 ( 2 hom., cov: 32)
Exomes 𝑓: 0.0028 ( 2 hom. )
Consequence
HGF
NM_000601.6 3_prime_UTR
NM_000601.6 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.533
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=-0.82).
BS2
High Homozygotes in GnomAd4 at 2 AR gene
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
|---|---|---|---|---|---|---|---|
| HGF | NM_000601.6 | c.*396A>T | 3_prime_UTR_variant | 18/18 | ENST00000222390.11 | ||
| HGF | NM_001010932.3 | c.*396A>T | 3_prime_UTR_variant | 18/18 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| HGF | ENST00000222390.11 | c.*396A>T | 3_prime_UTR_variant | 18/18 | 1 | NM_000601.6 | P4 | ||
| HGF | ENST00000457544.7 | c.*396A>T | 3_prime_UTR_variant | 18/18 | 1 | A1 |
Frequencies
GnomAD3 genomes 0.00312 AC: 473AN: 151668Hom.: 2 Cov.: 32
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GnomAD4 exome AF: 0.00275 AC: 238AN: 86398Hom.: 2 Cov.: 0 AF XY: 0.00312 AC XY: 127AN XY: 40722
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GnomAD4 genome 0.00312 AC: 474AN: 151786Hom.: 2 Cov.: 32 AF XY: 0.00278 AC XY: 206AN XY: 74190
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
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 | - - |
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