7-81713890-T-G

Position:

• chr7-81713890-T-G

Variant summary

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

The NM_000601.6(HGF):​c.1406-2371A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.746 in 151,854 control chromosomes in the GnomAD database, including 43,013 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 0.75 (43013 hom., cov: 31)
• Consequence: HGF NM_000601.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0490

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=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.849 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HGF	NM_000601.6	c.1406-2371A>C		intron_variant		ENST00000222390.11	NP_000592.3
HGF	NM_001010932.3	c.1391-2371A>C		intron_variant			NP_001010932.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HGF	ENST00000222390.11	c.1406-2371A>C		intron_variant		1	NM_000601.6	ENSP00000222390	P4
HGF	ENST00000457544.7	c.1391-2371A>C		intron_variant		1		ENSP00000391238	A1

Frequencies

GnomAD3 genomes AF: 0.746 AC: 113145 AN: 151736 Hom.: 42987 Cov.: 31

Gnomad AFR AF: 0.587

Gnomad AMI AF: 0.736

Gnomad AMR AF: 0.826

Gnomad ASJ AF: 0.861

Gnomad EAS AF: 0.854

Gnomad SAS AF: 0.870

Gnomad FIN AF: 0.781

Gnomad MID AF: 0.892

Gnomad NFE AF: 0.795

Gnomad OTH AF: 0.773

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

GnomAD4 genome AF: 0.746 AC: 113225 AN: 151854 Hom.: 43013 Cov.: 31 AF XY: 0.747 AC XY: 55485 AN XY: 74230

Gnomad4 AFR AF: 0.587

Gnomad4 AMR AF: 0.826

Gnomad4 ASJ AF: 0.861

Gnomad4 EAS AF: 0.854

Gnomad4 SAS AF: 0.871

Gnomad4 FIN AF: 0.781

Gnomad4 NFE AF: 0.795

Gnomad4 OTH AF: 0.772

Alfa AF: 0.718 Hom.: 3115

Bravo AF: 0.740

Asia WGS AF: 0.837 AC: 2911 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.6
DANN	Benign	0.81

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: rs6467866; hg19: chr7-81343206;