chr7-81717609-G-A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_000601.6(HGF):​c.1272-244C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.842 in 151,932 control chromosomes in the GnomAD database, including 54,055 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.84 ( 54055 hom., cov: 29)

Consequence

HGF
NM_000601.6 intron

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.469

Publications

5 publications found
Variant links:
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]
HGF Gene-Disease associations (from GenCC):
  • autosomal recessive nonsyndromic hearing loss 39
    Inheritance: AR, Unknown Classification: STRONG, LIMITED Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae), PanelApp Australia
  • nonsyndromic genetic hearing loss
    Inheritance: AR Classification: MODERATE Submitted by: ClinGen
  • hearing loss, autosomal recessive
    Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.97).
BP6
Variant 7-81717609-G-A is Benign according to our data. Variant chr7-81717609-G-A is described in ClinVar as [Benign]. Clinvar id is 1286880.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.91 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
HGFNM_000601.6 linkc.1272-244C>T intron_variant Intron 10 of 17 ENST00000222390.11 NP_000592.3 P14210-1
HGFNM_001010932.3 linkc.1257-244C>T intron_variant Intron 10 of 17 NP_001010932.1 P14210-3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
HGFENST00000222390.11 linkc.1272-244C>T intron_variant Intron 10 of 17 1 NM_000601.6 ENSP00000222390.5 P14210-1

Frequencies

GnomAD3 genomes
AF:
0.842
AC:
127759
AN:
151814
Hom.:
54007
Cov.:
29
show subpopulations
Gnomad AFR
AF:
0.918
Gnomad AMI
AF:
0.736
Gnomad AMR
AF:
0.866
Gnomad ASJ
AF:
0.864
Gnomad EAS
AF:
0.858
Gnomad SAS
AF:
0.872
Gnomad FIN
AF:
0.780
Gnomad MID
AF:
0.914
Gnomad NFE
AF:
0.796
Gnomad OTH
AF:
0.843
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.842
AC:
127866
AN:
151932
Hom.:
54055
Cov.:
29
AF XY:
0.841
AC XY:
62445
AN XY:
74224
show subpopulations
African (AFR)
AF:
0.917
AC:
38043
AN:
41464
American (AMR)
AF:
0.867
AC:
13219
AN:
15254
Ashkenazi Jewish (ASJ)
AF:
0.864
AC:
2999
AN:
3472
East Asian (EAS)
AF:
0.858
AC:
4409
AN:
5140
South Asian (SAS)
AF:
0.872
AC:
4198
AN:
4814
European-Finnish (FIN)
AF:
0.780
AC:
8209
AN:
10530
Middle Eastern (MID)
AF:
0.911
AC:
266
AN:
292
European-Non Finnish (NFE)
AF:
0.796
AC:
54087
AN:
67956
Other (OTH)
AF:
0.841
AC:
1768
AN:
2102
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.502
Heterozygous variant carriers
0
1011
2022
3034
4045
5056
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
888
1776
2664
3552
4440
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.815
Hom.:
64316
Bravo
AF:
0.850
Asia WGS
AF:
0.857
AC:
2980
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Nov 12, 2018
GeneDx
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.97
CADD
Benign
0.36
DANN
Benign
0.46
PhyloP100
-0.47
Mutation Taster
=100/0
polymorphism (auto)

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs5745720; hg19: chr7-81346925; API