NM_000601.6:c.1169-60C>T

Variant names:

• chr7-81720907-G-A
• rs10272030
• NM_000601.6:c.1169-60C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000601.6(HGF):​c.1169-60C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.822 in 913,342 control chromosomes in the GnomAD database, including 309,584 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.85 (55706 hom., cov: 34)
  • Exomes 𝑓: 0.82 (253878 hom.)
• Consequence: HGF NM_000601.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.489
• Publications: 12 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 7-81720907-G-A is Benign according to our data. Variant chr7-81720907-G-A is described in ClinVar as Benign. ClinVar VariationId is 1241564.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HGF	NM_000601.6	MANE Select	c.1169-60C>T		intron	N/A	NP_000592.3
	HGF	NM_001010932.3		c.1154-60C>T		intron	N/A	NP_001010932.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HGF	ENST00000222390.11	TSL:1 MANE Select	c.1169-60C>T		intron	N/A	ENSP00000222390.5
	HGF	ENST00000457544.7	TSL:1	c.1154-60C>T		intron	N/A	ENSP00000391238.2
	ENSG00000300407	ENST00000771413.1		n.117+20379G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.852 AC: 129697 AN: 152178 Hom.: 55652 Cov.: 34

Gnomad AFR AF: 0.955

Gnomad AMI AF: 0.735

Gnomad AMR AF: 0.870

Gnomad ASJ AF: 0.864

Gnomad EAS AF: 0.856

Gnomad SAS AF: 0.872

Gnomad FIN AF: 0.780

Gnomad MID AF: 0.918

Gnomad NFE AF: 0.796

Gnomad OTH AF: 0.851

GnomAD4 exome AF: 0.816 AC: 620687 AN: 761046 Hom.: 253878 AF XY: 0.817 AC XY: 330152 AN XY: 404190

African (AFR) AF: 0.956 AC: 18816 AN: 19680

American (AMR) AF: 0.890 AC: 36893 AN: 41474

Ashkenazi Jewish (ASJ) AF: 0.868 AC: 18706 AN: 21560

East Asian (EAS) AF: 0.881 AC: 31712 AN: 35984

South Asian (SAS) AF: 0.865 AC: 61153 AN: 70692

European-Finnish (FIN) AF: 0.791 AC: 40850 AN: 51656

Middle Eastern (MID) AF: 0.866 AC: 3209 AN: 3706

European-Non Finnish (NFE) AF: 0.790 AC: 378722 AN: 479172

Other (OTH) AF: 0.825 AC: 30626 AN: 37122

GnomAD4 genome AF: 0.852 AC: 129810 AN: 152296 Hom.: 55706 Cov.: 34 AF XY: 0.852 AC XY: 63426 AN XY: 74478

African (AFR) AF: 0.955 AC: 39693 AN: 41576

American (AMR) AF: 0.870 AC: 13319 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.864 AC: 2999 AN: 3472

East Asian (EAS) AF: 0.856 AC: 4436 AN: 5180

South Asian (SAS) AF: 0.873 AC: 4215 AN: 4830

European-Finnish (FIN) AF: 0.780 AC: 8274 AN: 10604

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

European-Non Finnish (NFE) AF: 0.796 AC: 54141 AN: 68010

Other (OTH) AF: 0.849 AC: 1794 AN: 2112

Alfa AF: 0.831 Hom.: 6679

Bravo AF: 0.862

Asia WGS AF: 0.858 AC: 2983 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Jun 22, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.13
DANN	Benign	0.52
PhyloP100		-0.49
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: rs10272030; hg19: chr7-81350223;