Variant 7-81702114-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_000601.6(HGF):c.*467A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0177 in 212,150 control chromosomes in the GnomAD database, including 142 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.023 ( 131 hom., cov: 32)

Exomes 𝑓: 0.0043 ( 11 hom. )

Consequence

HGF
NM_000601.6 3_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.806

Variant links:

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]

HGF links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BP6

Variant 7-81702114-T-C is Benign according to our data. Variant chr7-81702114-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 369591.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0759 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HGF	NM_000601.6 linkuse as main transcript	c.*467A>G		3_prime_UTR_variant	18/18	ENST00000222390.11	NP_000592.3	P14210-1
HGF	NM_001010932.3 linkuse as main transcript	c.*467A>G		3_prime_UTR_variant	18/18		NP_001010932.1	P14210-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HGF	ENST00000222390 linkuse as main transcript	c.*467A>G		3_prime_UTR_variant	18/18	1	NM_000601.6	ENSP00000222390.5		P14210-1
HGF	ENST00000457544.7 linkuse as main transcript	c.*467A>G		downstream_gene_variant		1		ENSP00000391238.2		P14210-3

Frequencies

GnomAD3 genomes

AF:

0.0230

AC:

3493

AN:

151598

Hom.:

131

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0785

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0122

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000236

Gnomad OTH

AF:

0.0206

GnomAD4 exome

AF:

0.00434

AC:

262

AN:

60434

Hom.:

Cov.:

AF XY:

0.00396

AC XY:

114

AN XY:

28820

show subpopulations

Gnomad4 AFR exome

AF:

0.0829

Gnomad4 AMR exome

AF:

0.00609

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000273

Gnomad4 OTH exome

AF:

0.00899

GnomAD4 genome

AF:

0.0230

AC:

3490

AN:

151716

Hom.:

131

Cov.:

AF XY:

0.0220

AC XY:

1630

AN XY:

74164

show subpopulations

Gnomad4 AFR

AF:

0.0782

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:

0.0204

Alfa

AF:

0.00487

Hom.:

Bravo

AF:

0.0266

Asia WGS

AF:

0.00433

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Nonsyndromic Hearing Loss, Mixed

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

DANN

Benign

0.84

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over