7-81702185-T-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_000601.6(HGF):c.*396A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00299 in 238,184 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0031 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0028 (2 hom.)
• Consequence: HGF NM_000601.6 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.533

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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BS2: High Homozygotes in GnomAd at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HGF	NM_000601.6	c.*396A>T		3_prime_UTR_variant	18/18	ENST00000222390.11
HGF	NM_001010932.3	c.*396A>T		3_prime_UTR_variant	18/18

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HGF	ENST00000222390.11	c.*396A>T		3_prime_UTR_variant	18/18	1	NM_000601.6	P4
HGF	ENST00000457544.7	c.*396A>T		3_prime_UTR_variant	18/18	1		A1

Frequencies

GnomAD3 genomes AF: 0.00312 AC: 473 AN: 151668 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.00109

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00258

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.00226

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00523

Gnomad OTH AF: 0.00191

GnomAD4 exome AF: 0.00275 AC: 238 AN: 86398 Hom.: 2 Cov.: 0 AF XY: 0.00312 AC XY: 127 AN XY: 40722

Gnomad4 AFR exome AF: 0.000278

Gnomad4 AMR exome AF: 0.00247

Gnomad4 ASJ exome AF: 0.000210

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00141

Gnomad4 FIN exome AF: 0.00207

Gnomad4 NFE exome AF: 0.00387

Gnomad4 OTH exome AF: 0.00239

GnomAD4 genome AF: 0.00312 AC: 474 AN: 151786 Hom.: 2 Cov.: 32 AF XY: 0.00278 AC XY: 206 AN XY: 74190

Gnomad4 AFR AF: 0.00108

Gnomad4 AMR AF: 0.00264

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00124

Gnomad4 FIN AF: 0.00226

Gnomad4 NFE AF: 0.00523

Gnomad4 OTH AF: 0.00189

Alfa AF: 0.00302 Hom.: 0

Bravo AF: 0.00313

Asia WGS AF: 0.000289 AC: 1 AN: 3476

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Nonsyndromic Hearing Loss, Mixed Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	6.0
Dann	Benign	0.68

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: rs182057547; hg19: chr7-81331501;