rs5745692

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_000601.6(HGF):​c.1040+655G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0229 in 152,286 control chromosomes in the GnomAD database, including 64 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.023 ( 64 hom., cov: 33)

Consequence

HGF
NM_000601.6 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0900
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.8).
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0229 (3481/152286) while in subpopulation NFE AF= 0.0358 (2433/68016). AF 95% confidence interval is 0.0346. There are 64 homozygotes in gnomad4. There are 1659 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 64 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
HGFNM_000601.6 linkuse as main transcriptc.1040+655G>C intron_variant ENST00000222390.11
HGFNM_001010932.3 linkuse as main transcriptc.1025+655G>C intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
HGFENST00000222390.11 linkuse as main transcriptc.1040+655G>C intron_variant 1 NM_000601.6 P4P14210-1
HGFENST00000457544.7 linkuse as main transcriptc.1025+655G>C intron_variant 1 A1P14210-3

Frequencies

GnomAD3 genomes
AF:
0.0229
AC:
3483
AN:
152168
Hom.:
63
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00550
Gnomad AMI
AF:
0.0220
Gnomad AMR
AF:
0.0242
Gnomad ASJ
AF:
0.0167
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.0114
Gnomad FIN
AF:
0.0238
Gnomad MID
AF:
0.0285
Gnomad NFE
AF:
0.0358
Gnomad OTH
AF:
0.0272
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.0229
AC:
3481
AN:
152286
Hom.:
64
Cov.:
33
AF XY:
0.0223
AC XY:
1659
AN XY:
74466
show subpopulations
Gnomad4 AFR
AF:
0.00549
Gnomad4 AMR
AF:
0.0242
Gnomad4 ASJ
AF:
0.0167
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.0116
Gnomad4 FIN
AF:
0.0238
Gnomad4 NFE
AF:
0.0358
Gnomad4 OTH
AF:
0.0274
Alfa
AF:
0.0305
Hom.:
11
Bravo
AF:
0.0228
Asia WGS
AF:
0.00318
AC:
11
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.80
CADD
Benign
5.3
DANN
Benign
0.56

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs5745692; hg19: chr7-81358266; API