7-81702807-G-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_000601.6(HGF):c.2011-50C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00235 in 1,474,030 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0019 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0024 (8 hom.)
• Consequence: HGF NM_000601.6 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0320

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 7-81702807-G-T is Benign according to our data. Variant chr7-81702807-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 1186051.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HGF	NM_000601.6	c.2011-50C>A		intron_variant		ENST00000222390.11
HGF	NM_001010932.3	c.1996-50C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HGF	ENST00000222390.11	c.2011-50C>A		intron_variant		1	NM_000601.6	P4
HGF	ENST00000457544.7	c.1996-50C>A		intron_variant		1		A1

Frequencies

GnomAD3 genomes AF: 0.00189 AC: 286 AN: 151420 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000387

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00258

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00125

Gnomad FIN AF: 0.00274

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00282

Gnomad OTH AF: 0.00240

GnomAD3 exomes AF: 0.00242 AC: 580 AN: 240076 Hom.: 2 AF XY: 0.00257 AC XY: 336 AN XY: 130646

Gnomad AFR exome AF: 0.000411

Gnomad AMR exome AF: 0.00438

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000577

Gnomad SAS exome AF: 0.000571

Gnomad FIN exome AF: 0.00216

Gnomad NFE exome AF: 0.00320

Gnomad OTH exome AF: 0.00307

GnomAD4 exome AF: 0.00240 AC: 3177 AN: 1322492 Hom.: 8 Cov.: 21 AF XY: 0.00244 AC XY: 1624 AN XY: 665698

Gnomad4 AFR exome AF: 0.000333

Gnomad4 AMR exome AF: 0.00431

Gnomad4 ASJ exome AF: 0.0000399

Gnomad4 EAS exome AF: 0.0000261

Gnomad4 SAS exome AF: 0.000896

Gnomad4 FIN exome AF: 0.00283

Gnomad4 NFE exome AF: 0.00265

Gnomad4 OTH exome AF: 0.00219

GnomAD4 genome AF: 0.00189 AC: 286 AN: 151538 Hom.: 0 Cov.: 32 AF XY: 0.00189 AC XY: 140 AN XY: 74060

Gnomad4 AFR AF: 0.000386

Gnomad4 AMR AF: 0.00258

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00125

Gnomad4 FIN AF: 0.00274

Gnomad4 NFE AF: 0.00282

Gnomad4 OTH AF: 0.00237

Alfa AF: 0.00202 Hom.: 0

Bravo AF: 0.00193

Asia WGS AF: 0.000577 AC: 2 AN: 3478

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

Jun 12, 2020

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	0.47
Dann	Benign	0.49

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: rs78291552; hg19: chr7-81332123;