rs2040965

Variant names:

• chr7-81723270-G-A
• rs2040965
• NM_000601.6:c.1169-2423C>T

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 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, Unknown Classification: STRONG, LIMITED Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae), PanelApp Australia
• 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=-0.98).
• 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 rank	MANE	Protein	UniProt
HGF	NM_000601.6	c.1169-2423C>T		intron_variant	Intron 9 of 17	ENST00000222390.11	NP_000592.3
HGF	NM_001010932.3	c.1154-2423C>T		intron_variant	Intron 9 of 17		NP_001010932.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HGF	ENST00000222390.11	c.1169-2423C>T		intron_variant	Intron 9 of 17	1	NM_000601.6	ENSP00000222390.5

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

African (AFR) AF: 0.811 AC: 33640 AN: 41484

American (AMR) AF: 0.850 AC: 12972 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.885 AC: 3074 AN: 3472

East Asian (EAS) AF: 0.854 AC: 4421 AN: 5178

South Asian (SAS) AF: 0.870 AC: 4192 AN: 4820

European-Finnish (FIN) AF: 0.807 AC: 8512 AN: 10554

Middle Eastern (MID) AF: 0.900 AC: 261 AN: 290

European-Non Finnish (NFE) AF: 0.807 AC: 54876 AN: 67960

Other (OTH) AF: 0.820 AC: 1731 AN: 2110

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
PhyloP100		-0.84
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: rs2040965; hg19: chr7-81352586;