7-81720096-T-C

Variant names:

• chr7-81720096-T-C
• rs5745709
• NM_000601.6:c.1271+649A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000601.6(HGF):​c.1271+649A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.852 in 152,214 control chromosomes in the GnomAD database, including 55,684 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 0.85 (55684 hom., cov: 32)
• Consequence: HGF NM_000601.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.39
• Publications: 8 publications found

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]

HGF Gene-Disease associations (from GenCC):

• autosomal recessive nonsyndromic hearing loss 39

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
• nonsyndromic genetic hearing loss

  Inheritance: AR Classification: MODERATE Submitted by: ClinGen
• hearing loss, autosomal recessive

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000300407 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.947 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000601.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HGF	NM_000601.6	MANE Select	c.1271+649A>G		intron	N/A	NP_000592.3
	HGF	NM_001010932.3		c.1256+649A>G		intron	N/A	NP_001010932.1	P14210-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HGF	ENST00000222390.11	TSL:1 MANE Select	c.1271+649A>G		intron	N/A	ENSP00000222390.5	P14210-1
	HGF	ENST00000457544.7	TSL:1	c.1256+649A>G		intron	N/A	ENSP00000391238.2	P14210-3
	ENSG00000300407	ENST00000771413.1		n.117+19568T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.852 AC: 129629 AN: 152096 Hom.: 55630 Cov.: 32

Gnomad AFR AF: 0.955

Gnomad AMI AF: 0.735

Gnomad AMR AF: 0.870

Gnomad ASJ AF: 0.864

Gnomad EAS AF: 0.858

Gnomad SAS AF: 0.872

Gnomad FIN AF: 0.780

Gnomad MID AF: 0.918

Gnomad NFE AF: 0.796

Gnomad OTH AF: 0.853

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

GnomAD4 genome AF: 0.852 AC: 129742 AN: 152214 Hom.: 55684 Cov.: 32 AF XY: 0.852 AC XY: 63379 AN XY: 74416

African (AFR) AF: 0.955 AC: 39668 AN: 41546

American (AMR) AF: 0.870 AC: 13313 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.864 AC: 2997 AN: 3470

East Asian (EAS) AF: 0.858 AC: 4438 AN: 5172

South Asian (SAS) AF: 0.873 AC: 4209 AN: 4824

European-Finnish (FIN) AF: 0.780 AC: 8263 AN: 10590

Middle Eastern (MID) AF: 0.915 AC: 269 AN: 294

European-Non Finnish (NFE) AF: 0.796 AC: 54118 AN: 67992

Other (OTH) AF: 0.851 AC: 1797 AN: 2112

Alfa AF: 0.816 Hom.: 23168

Bravo AF: 0.862

Asia WGS AF: 0.860 AC: 2990 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.71
DANN	Benign	0.50
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs5745709; hg19: chr7-81349412;