7-81702835-G-T

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.2011-78C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00516 in 1,173,910 control chromosomes in the GnomAD database, including 224 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.023 (132 hom., cov: 32)
  • Exomes 𝑓: 0.0025 (92 hom.)
• Consequence: HGF NM_000601.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.116

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=-0.81).
• BP6: Variant 7-81702835-G-T is Benign according to our data. Variant chr7-81702835-G-T is described in ClinVar as [Benign]. Clinvar id is 1244067.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0762 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HGF	NM_000601.6	c.2011-78C>A		intron_variant		ENST00000222390.11
HGF	NM_001010932.3	c.1996-78C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HGF	ENST00000222390.11	c.2011-78C>A		intron_variant		1	NM_000601.6	P4
HGF	ENST00000457544.7	c.1996-78C>A		intron_variant		1		A1

Frequencies

GnomAD3 genomes AF: 0.0231 AC: 3502 AN: 151512 Hom.: 132 Cov.: 32

Gnomad AFR AF: 0.0788

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0121

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.000236

Gnomad OTH AF: 0.0202

GnomAD4 exome AF: 0.00250 AC: 2558 AN: 1022280 Hom.: 92 AF XY: 0.00211 AC XY: 1113 AN XY: 526958

Gnomad4 AFR exome AF: 0.0824

Gnomad4 AMR exome AF: 0.00523

Gnomad4 ASJ exome AF: 0.0000879

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000678

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000174

Gnomad4 OTH exome AF: 0.00598

GnomAD4 genome AF: 0.0231 AC: 3499 AN: 151630 Hom.: 132 Cov.: 32 AF XY: 0.0221 AC XY: 1636 AN XY: 74110

Gnomad4 AFR AF: 0.0785

Gnomad4 AMR AF: 0.0121

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000622

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000236

Gnomad4 OTH AF: 0.0200

Alfa AF: 0.00209 Hom.: 0

Bravo AF: 0.0266

Asia WGS AF: 0.00433 AC: 16 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 29, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	11
Dann	Benign	0.56

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: rs5745766; hg19: chr7-81332151;