rs7804865

Positions:

• chr7-81746538-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000601.6(HGF):​c.626-1418C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.809 in 152,110 control chromosomes in the GnomAD database, including 50,034 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 0.81 (50034 hom., cov: 32)
• Consequence: HGF NM_000601.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.328

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.87 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HGF	NM_000601.6	c.626-1418C>T		intron_variant		ENST00000222390.11	NP_000592.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HGF	ENST00000222390.11	c.626-1418C>T		intron_variant		1	NM_000601.6	ENSP00000222390.5
HGF	ENST00000457544.7	c.611-1418C>T		intron_variant		1		ENSP00000391238.2
HGF	ENST00000444829.7	c.626-1418C>T		intron_variant		1		ENSP00000389854.2
HGF	ENST00000453411.6	c.611-1418C>T		intron_variant		1		ENSP00000408270.1

Frequencies

GnomAD3 genomes AF: 0.809 AC: 122915 AN: 151992 Hom.: 49988 Cov.: 32

Gnomad AFR AF: 0.878

Gnomad AMI AF: 0.626

Gnomad AMR AF: 0.845

Gnomad ASJ AF: 0.866

Gnomad EAS AF: 0.839

Gnomad SAS AF: 0.866

Gnomad FIN AF: 0.726

Gnomad MID AF: 0.902

Gnomad NFE AF: 0.764

Gnomad OTH AF: 0.824

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.809 AC: 123017 AN: 152110 Hom.: 50034 Cov.: 32 AF XY: 0.808 AC XY: 60064 AN XY: 74344

Gnomad4 AFR AF: 0.878

Gnomad4 AMR AF: 0.845

Gnomad4 ASJ AF: 0.866

Gnomad4 EAS AF: 0.839

Gnomad4 SAS AF: 0.866

Gnomad4 FIN AF: 0.726

Gnomad4 NFE AF: 0.764

Gnomad4 OTH AF: 0.824

Alfa AF: 0.791 Hom.: 10540

Bravo AF: 0.819

Asia WGS AF: 0.849 AC: 2953 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	3.1
DANN	Benign	0.60

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

Other links and lift over

dbSNP: rs7804865; hg19: chr7-81375854;