rs12707453

chr7-81740103-A-G

Variant summary

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

The NM_000601.6(HGF):c.865+3250T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.141 in 152,202 control chromosomes in the GnomAD database, including 1,925 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 0.14 (1925 hom., cov: 31)
• Consequence: HGF NM_000601.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.794

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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.298 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HGF	NM_000601.6	c.865+3250T>C		intron_variant		ENST00000222390.11
HGF	NM_001010932.3	c.850+3250T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HGF	ENST00000222390.11	c.865+3250T>C		intron_variant		1	NM_000601.6	P4
HGF	ENST00000457544.7	c.850+3250T>C		intron_variant		1		A1

Frequencies

GnomAD3 genomes AF: 0.141 AC: 21425 AN: 152084 Hom.: 1923 Cov.: 31

Gnomad AFR AF: 0.0369

Gnomad AMI AF: 0.113

Gnomad AMR AF: 0.187

Gnomad ASJ AF: 0.246

Gnomad EAS AF: 0.310

Gnomad SAS AF: 0.227

Gnomad FIN AF: 0.0836

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.177

Gnomad OTH AF: 0.175

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

GnomAD4 genome AF: 0.141 AC: 21409 AN: 152202 Hom.: 1925 Cov.: 31 AF XY: 0.139 AC XY: 10337 AN XY: 74420

Gnomad4 AFR AF: 0.0368

Gnomad4 AMR AF: 0.187

Gnomad4 ASJ AF: 0.246

Gnomad4 EAS AF: 0.311

Gnomad4 SAS AF: 0.228

Gnomad4 FIN AF: 0.0836

Gnomad4 NFE AF: 0.177

Gnomad4 OTH AF: 0.172

Alfa AF: 0.177 Hom.: 3187

Bravo AF: 0.147

Asia WGS AF: 0.218 AC: 758 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	3.9
Dann	Benign	0.72

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: rs12707453; hg19: chr7-81369419;