7-81720892-A-G

Position:

• chr7-81720892-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000601.6(HGF):​c.1169-45T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.82 in 993,120 control chromosomes in the GnomAD database, including 335,429 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.85 (55678 hom., cov: 33)
  • Exomes 𝑓: 0.81 (279751 hom.)
• Consequence: HGF NM_000601.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.41

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BP6: Variant 7-81720892-A-G is Benign according to our data. Variant chr7-81720892-A-G is described in ClinVar as [Benign]. Clinvar id is 1246790.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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HGF	NM_000601.6	c.1169-45T>C		intron_variant		ENST00000222390.11	NP_000592.3
HGF	NM_001010932.3	c.1154-45T>C		intron_variant			NP_001010932.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HGF	ENST00000222390.11	c.1169-45T>C		intron_variant		1	NM_000601.6	ENSP00000222390.5
HGF	ENST00000457544.7	c.1154-45T>C		intron_variant		1		ENSP00000391238.2

Frequencies

GnomAD3 genomes AF: 0.852 AC: 129635 AN: 152116 Hom.: 55624 Cov.: 33

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: 0.873

Gnomad FIN AF: 0.780

Gnomad MID AF: 0.918

Gnomad NFE AF: 0.796

Gnomad OTH AF: 0.851

GnomAD3 exomes AF: 0.835 AC: 201034 AN: 240720 Hom.: 84123 AF XY: 0.833 AC XY: 108475 AN XY: 130234

Gnomad AFR exome AF: 0.956

Gnomad AMR exome AF: 0.891

Gnomad ASJ exome AF: 0.868

Gnomad EAS exome AF: 0.854

Gnomad SAS exome AF: 0.866

Gnomad FIN exome AF: 0.791

Gnomad NFE exome AF: 0.795

Gnomad OTH exome AF: 0.824

GnomAD4 exome AF: 0.814 AC: 684405 AN: 840886 Hom.: 279751 Cov.: 11 AF XY: 0.815 AC XY: 361818 AN XY: 443766

Gnomad4 AFR exome AF: 0.957

Gnomad4 AMR exome AF: 0.889

Gnomad4 ASJ exome AF: 0.867

Gnomad4 EAS exome AF: 0.881

Gnomad4 SAS exome AF: 0.865

Gnomad4 FIN exome AF: 0.791

Gnomad4 NFE exome AF: 0.790

Gnomad4 OTH exome AF: 0.825

GnomAD4 genome AF: 0.852 AC: 129748 AN: 152234 Hom.: 55678 Cov.: 33 AF XY: 0.852 AC XY: 63369 AN XY: 74414

Gnomad4 AFR AF: 0.955

Gnomad4 AMR AF: 0.870

Gnomad4 ASJ AF: 0.864

Gnomad4 EAS AF: 0.856

Gnomad4 SAS AF: 0.873

Gnomad4 FIN AF: 0.780

Gnomad4 NFE AF: 0.796

Gnomad4 OTH AF: 0.849

Alfa AF: 0.820 Hom.: 7037

Bravo AF: 0.862

Asia WGS AF: 0.857 AC: 2982 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 22, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.046
DANN	Benign	0.32

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs12536657; hg19: chr7-81350208;