rs2040965

Positions:

• chr7-81723270-G-A
• chr7-81723270-G-C
• chr7-81723270-G-T

Variant summary

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

The NM_000601.6(HGF):​c.1169-2423C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.818 in 152,044 control chromosomes in the GnomAD database, including 50,884 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 (50884 hom., cov: 32)
• Consequence: HGF NM_000601.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.841

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=-0.98).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.848 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HGF	NM_000601.6	c.1169-2423C>T		intron_variant		ENST00000222390.11	NP_000592.3
HGF	NM_001010932.3	c.1154-2423C>T		intron_variant			NP_001010932.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HGF	ENST00000222390.11	c.1169-2423C>T		intron_variant		1	NM_000601.6	ENSP00000222390	P4
HGF	ENST00000457544.7	c.1154-2423C>T		intron_variant		1		ENSP00000391238	A1

Frequencies

GnomAD3 genomes AF: 0.818 AC: 124219 AN: 151928 Hom.: 50839 Cov.: 32

Gnomad AFR AF: 0.811

Gnomad AMI AF: 0.705

Gnomad AMR AF: 0.850

Gnomad ASJ AF: 0.885

Gnomad EAS AF: 0.854

Gnomad SAS AF: 0.870

Gnomad FIN AF: 0.807

Gnomad MID AF: 0.904

Gnomad NFE AF: 0.807

Gnomad OTH AF: 0.822

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

GnomAD4 genome AF: 0.818 AC: 124322 AN: 152044 Hom.: 50884 Cov.: 32 AF XY: 0.818 AC XY: 60799 AN XY: 74290

Gnomad4 AFR AF: 0.811

Gnomad4 AMR AF: 0.850

Gnomad4 ASJ AF: 0.885

Gnomad4 EAS AF: 0.854

Gnomad4 SAS AF: 0.870

Gnomad4 FIN AF: 0.807

Gnomad4 NFE AF: 0.807

Gnomad4 OTH AF: 0.820

Alfa AF: 0.821 Hom.: 6501

Bravo AF: 0.819

Asia WGS AF: 0.852 AC: 2962 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.87
DANN	Benign	0.53

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: rs2040965; hg19: chr7-81352586;