chr7-81706144-C-T

Position:

• chr7-81706144-C-T

Variant summary

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

The ENST00000222390.11(HGF):​c.1757+143G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.288 in 743,018 control chromosomes in the GnomAD database, including 31,986 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.25 (5180 hom., cov: 31)
  • Exomes 𝑓: 0.30 (26806 hom.)
• Consequence: HGF ENST00000222390.11 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.49

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=-0.9).
• BP6: Variant 7-81706144-C-T is Benign according to our data. Variant chr7-81706144-C-T is described in ClinVar as [Benign]. Clinvar id is 1239121.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.356 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HGF	NM_000601.6	c.1757+143G>A		intron_variant		ENST00000222390.11	NP_000592.3
HGF	NM_001010932.3	c.1742+143G>A		intron_variant			NP_001010932.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HGF	ENST00000222390.11	c.1757+143G>A		intron_variant		1	NM_000601.6	ENSP00000222390	P4
HGF	ENST00000457544.7	c.1742+143G>A		intron_variant		1		ENSP00000391238	A1

Frequencies

GnomAD3 genomes AF: 0.253 AC: 38298 AN: 151538 Hom.: 5177 Cov.: 31

Gnomad AFR AF: 0.148

Gnomad AMI AF: 0.299

Gnomad AMR AF: 0.268

Gnomad ASJ AF: 0.292

Gnomad EAS AF: 0.332

Gnomad SAS AF: 0.369

Gnomad FIN AF: 0.256

Gnomad MID AF: 0.369

Gnomad NFE AF: 0.295

Gnomad OTH AF: 0.267

GnomAD4 exome AF: 0.297 AC: 175532 AN: 591362 Hom.: 26806 AF XY: 0.299 AC XY: 94443 AN XY: 315664

Gnomad4 AFR exome AF: 0.141

Gnomad4 AMR exome AF: 0.260

Gnomad4 ASJ exome AF: 0.309

Gnomad4 EAS exome AF: 0.339

Gnomad4 SAS exome AF: 0.341

Gnomad4 FIN exome AF: 0.260

Gnomad4 NFE exome AF: 0.299

Gnomad4 OTH exome AF: 0.288

GnomAD4 genome AF: 0.253 AC: 38297 AN: 151656 Hom.: 5180 Cov.: 31 AF XY: 0.253 AC XY: 18732 AN XY: 74082

Gnomad4 AFR AF: 0.148

Gnomad4 AMR AF: 0.267

Gnomad4 ASJ AF: 0.292

Gnomad4 EAS AF: 0.332

Gnomad4 SAS AF: 0.370

Gnomad4 FIN AF: 0.256

Gnomad4 NFE AF: 0.295

Gnomad4 OTH AF: 0.265

Alfa AF: 0.289 Hom.: 8723

Bravo AF: 0.250

Asia WGS AF: 0.315 AC: 1094 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

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.10
DANN	Benign	0.55

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: rs5745752; hg19: chr7-81335460;