7-81701064-C-G

Variant names:

• chr7-81701064-C-G
• rs4732402
• NM_000601.6:c.*1517G>C

Variant summary

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

The NM_000601.6(HGF):​c.*1517G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.726 in 151,386 control chromosomes in the GnomAD database, including 41,258 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 0.73 (41257 hom., cov: 32)
  • Exomes 𝑓: 1.0 (1 hom.)
• Consequence: HGF NM_000601.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.39
• 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 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=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.847 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.*1517G>C		3_prime_UTR	Exon 18 of 18	NP_000592.3
	HGF	NM_001010932.3		c.*1517G>C		3_prime_UTR	Exon 18 of 18	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.*1517G>C		3_prime_UTR	Exon 18 of 18	ENSP00000222390.5	P14210-1
	ENSG00000300407	ENST00000771416.1		n.827C>G		non_coding_transcript_exon	Exon 2 of 2
	ENSG00000300407	ENST00000771413.1		n.117+536C>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.726 AC: 109889 AN: 151266 Hom.: 41236 Cov.: 32

Gnomad AFR AF: 0.521

Gnomad AMI AF: 0.736

Gnomad AMR AF: 0.817

Gnomad ASJ AF: 0.872

Gnomad EAS AF: 0.859

Gnomad SAS AF: 0.868

Gnomad FIN AF: 0.779

Gnomad MID AF: 0.889

Gnomad NFE AF: 0.794

Gnomad OTH AF: 0.765

GnomAD4 exome AF: 1.00 AC: 2 AN: 2 Hom.: 1 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 2 AN: 2

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.726 AC: 109956 AN: 151384 Hom.: 41257 Cov.: 32 AF XY: 0.729 AC XY: 53977 AN XY: 73994

African (AFR) AF: 0.521 AC: 21579 AN: 41398

American (AMR) AF: 0.817 AC: 12368 AN: 15134

Ashkenazi Jewish (ASJ) AF: 0.872 AC: 3016 AN: 3460

East Asian (EAS) AF: 0.859 AC: 4412 AN: 5138

South Asian (SAS) AF: 0.869 AC: 4193 AN: 4826

European-Finnish (FIN) AF: 0.779 AC: 8233 AN: 10566

Middle Eastern (MID) AF: 0.884 AC: 258 AN: 292

European-Non Finnish (NFE) AF: 0.794 AC: 53628 AN: 67568

Other (OTH) AF: 0.764 AC: 1599 AN: 2092

Alfa AF: 0.700 Hom.: 2232

Bravo AF: 0.718

Asia WGS AF: 0.834 AC: 2901 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.3
DANN	Benign	0.74
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: rs4732402; hg19: chr7-81330380;