chr7-81699165-A-T

Variant names:

• chr7-81699165-A-T
• rs1743
• NM_000601.6:c.*3416T>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_000601.6(HGF):​c.*3416T>A 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 151,258 control chromosomes in the GnomAD database, including 41,232 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 (41232 hom., cov: 31)
  • Failed GnomAD Quality Control
• Consequence: HGF NM_000601.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.432
• Publications: 6 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• 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.*3416T>A		3_prime_UTR	Exon 18 of 18	NP_000592.3
	HGF	NM_001010932.3		c.*3416T>A		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.*3416T>A		3_prime_UTR	Exon 18 of 18	ENSP00000222390.5	P14210-1
	ENSG00000300407	ENST00000771413.1		n.77-1323A>T		intron	N/A
	ENSG00000300407	ENST00000771414.1		n.131-1323A>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.726 AC: 109794 AN: 151142 Hom.: 41211 Cov.: 31

Gnomad AFR AF: 0.520

Gnomad AMI AF: 0.736

Gnomad AMR AF: 0.817

Gnomad ASJ AF: 0.872

Gnomad EAS AF: 0.858

Gnomad SAS AF: 0.869

Gnomad FIN AF: 0.780

Gnomad MID AF: 0.885

Gnomad NFE AF: 0.794

Gnomad OTH AF: 0.766

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

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: 109860 AN: 151258 Hom.: 41232 Cov.: 31 AF XY: 0.729 AC XY: 53853 AN XY: 73844

African (AFR) AF: 0.520 AC: 21511 AN: 41350

American (AMR) AF: 0.817 AC: 12377 AN: 15148

Ashkenazi Jewish (ASJ) AF: 0.872 AC: 3007 AN: 3450

East Asian (EAS) AF: 0.858 AC: 4405 AN: 5132

South Asian (SAS) AF: 0.869 AC: 4186 AN: 4816

European-Finnish (FIN) AF: 0.780 AC: 8196 AN: 10512

Middle Eastern (MID) AF: 0.880 AC: 257 AN: 292

European-Non Finnish (NFE) AF: 0.794 AC: 53640 AN: 67542

Other (OTH) AF: 0.765 AC: 1611 AN: 2106

Alfa AF: 0.758 Hom.: 5233

Bravo AF: 0.718

Asia WGS AF: 0.833 AC: 2883 AN: 3460

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	9.1
DANN	Benign	0.77
PhyloP100		0.43
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: rs1743; hg19: chr7-81328481;