chr7-81735119-C-G

Position:

• chr7-81735119-C-G

Variant summary

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

The NM_000601.6(HGF):​c.866-5340G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.822 in 152,048 control chromosomes in the GnomAD database, including 51,873 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 0.82 (51873 hom., cov: 31)
• Consequence: HGF NM_000601.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0630

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.917 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HGF	NM_000601.6	c.866-5340G>C		intron_variant		ENST00000222390.11	NP_000592.3
HGF	NM_001010932.3	c.851-5340G>C		intron_variant			NP_001010932.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HGF	ENST00000222390.11	c.866-5340G>C		intron_variant		1	NM_000601.6	ENSP00000222390.5
HGF	ENST00000457544.7	c.851-5340G>C		intron_variant		1		ENSP00000391238.2

Frequencies

GnomAD3 genomes AF: 0.822 AC: 124914 AN: 151928 Hom.: 51822 Cov.: 31

Gnomad AFR AF: 0.925

Gnomad AMI AF: 0.627

Gnomad AMR AF: 0.849

Gnomad ASJ AF: 0.866

Gnomad EAS AF: 0.839

Gnomad SAS AF: 0.866

Gnomad FIN AF: 0.725

Gnomad MID AF: 0.905

Gnomad NFE AF: 0.764

Gnomad OTH AF: 0.832

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

GnomAD4 genome AF: 0.822 AC: 125023 AN: 152048 Hom.: 51873 Cov.: 31 AF XY: 0.821 AC XY: 61024 AN XY: 74316

Gnomad4 AFR AF: 0.925

Gnomad4 AMR AF: 0.849

Gnomad4 ASJ AF: 0.866

Gnomad4 EAS AF: 0.839

Gnomad4 SAS AF: 0.866

Gnomad4 FIN AF: 0.725

Gnomad4 NFE AF: 0.764

Gnomad4 OTH AF: 0.833

Alfa AF: 0.713 Hom.: 1485

Bravo AF: 0.835

Asia WGS AF: 0.849 AC: 2954 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.23
DANN	Benign	0.35

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: rs17427817; hg19: chr7-81364435;