rs2887069

Positions:

• chr7-81725750-G-A

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.1168+140C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.814 in 939,402 control chromosomes in the GnomAD database, including 311,848 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.81 (50010 hom., cov: 32)
  • Exomes 𝑓: 0.81 (261838 hom.)
• Consequence: HGF NM_000601.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0170

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=-0.89).
• BP6: Variant 7-81725750-G-A is Benign according to our data. Variant chr7-81725750-G-A is described in ClinVar as [Benign]. Clinvar id is 1269325.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.846 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HGF	NM_000601.6	c.1168+140C>T		intron_variant		ENST00000222390.11
HGF	NM_001010932.3	c.1153+140C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HGF	ENST00000222390.11	c.1168+140C>T		intron_variant		1	NM_000601.6	P4
HGF	ENST00000457544.7	c.1153+140C>T		intron_variant		1		A1

Frequencies

GnomAD3 genomes AF: 0.810 AC: 123164 AN: 152000 Hom.: 49967 Cov.: 32

Gnomad AFR AF: 0.809

Gnomad AMI AF: 0.700

Gnomad AMR AF: 0.845

Gnomad ASJ AF: 0.875

Gnomad EAS AF: 0.854

Gnomad SAS AF: 0.868

Gnomad FIN AF: 0.802

Gnomad MID AF: 0.902

Gnomad NFE AF: 0.795

Gnomad OTH AF: 0.815

GnomAD4 exome AF: 0.815 AC: 641417 AN: 787284 Hom.: 261838 AF XY: 0.816 AC XY: 340395 AN XY: 417026

Gnomad4 AFR exome AF: 0.805

Gnomad4 AMR exome AF: 0.878

Gnomad4 ASJ exome AF: 0.879

Gnomad4 EAS exome AF: 0.882

Gnomad4 SAS exome AF: 0.862

Gnomad4 FIN exome AF: 0.812

Gnomad4 NFE exome AF: 0.795

Gnomad4 OTH exome AF: 0.816

GnomAD4 genome AF: 0.810 AC: 123266 AN: 152118 Hom.: 50010 Cov.: 32 AF XY: 0.812 AC XY: 60342 AN XY: 74342

Gnomad4 AFR AF: 0.810

Gnomad4 AMR AF: 0.845

Gnomad4 ASJ AF: 0.875

Gnomad4 EAS AF: 0.853

Gnomad4 SAS AF: 0.868

Gnomad4 FIN AF: 0.802

Gnomad4 NFE AF: 0.795

Gnomad4 OTH AF: 0.814

Alfa AF: 0.811 Hom.: 20333

Bravo AF: 0.812

Asia WGS AF: 0.850 AC: 2956 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	Mar 29, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.66
DANN	Benign	0.26

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: rs2887069; hg19: chr7-81355066;