chr7-81702897-T-C

Position:

• chr7-81702897-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000601.6(HGF):​c.2011-140A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.022 in 728,062 control chromosomes in the GnomAD database, including 306 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.018 (51 hom., cov: 32)
  • Exomes 𝑓: 0.023 (255 hom.)
• Consequence: HGF NM_000601.6 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.113

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 7-81702897-T-C is Benign according to our data. Variant chr7-81702897-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 1218721.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.081 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HGF	NM_000601.6	c.2011-140A>G		intron_variant		ENST00000222390.11	NP_000592.3
HGF	NM_001010932.3	c.1996-140A>G		intron_variant			NP_001010932.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HGF	ENST00000222390.11	c.2011-140A>G		intron_variant		1	NM_000601.6	ENSP00000222390.5
HGF	ENST00000457544.7	c.1996-140A>G		intron_variant		1		ENSP00000391238.2

Frequencies

GnomAD3 genomes AF: 0.0182 AC: 2764 AN: 151688 Hom.: 51 Cov.: 32

Gnomad AFR AF: 0.00645

Gnomad AMI AF: 0.0362

Gnomad AMR AF: 0.0280

Gnomad ASJ AF: 0.00492

Gnomad EAS AF: 0.0878

Gnomad SAS AF: 0.0269

Gnomad FIN AF: 0.00641

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0196

Gnomad OTH AF: 0.0196

GnomAD4 exome AF: 0.0231 AC: 13294 AN: 576258 Hom.: 255 AF XY: 0.0226 AC XY: 6918 AN XY: 306592

Gnomad4 AFR exome AF: 0.00476

Gnomad4 AMR exome AF: 0.0361

Gnomad4 ASJ exome AF: 0.00547

Gnomad4 EAS exome AF: 0.0843

Gnomad4 SAS exome AF: 0.0238

Gnomad4 FIN exome AF: 0.00656

Gnomad4 NFE exome AF: 0.0203

Gnomad4 OTH exome AF: 0.0223

GnomAD4 genome AF: 0.0182 AC: 2757 AN: 151804 Hom.: 51 Cov.: 32 AF XY: 0.0175 AC XY: 1296 AN XY: 74218

Gnomad4 AFR AF: 0.00643

Gnomad4 AMR AF: 0.0278

Gnomad4 ASJ AF: 0.00492

Gnomad4 EAS AF: 0.0877

Gnomad4 SAS AF: 0.0269

Gnomad4 FIN AF: 0.00641

Gnomad4 NFE AF: 0.0196

Gnomad4 OTH AF: 0.0184

Alfa AF: 0.0165 Hom.: 5

Bravo AF: 0.0206

Asia WGS AF: 0.0580 AC: 202 AN: 3476

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Dec 21, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.6
DANN	Benign	0.80

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

Publications

LitVar

Other links and lift over

dbSNP: rs5745765; hg19: chr7-81332213;