rs12536657

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000601.6(HGF):c.1169-45T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.82 in 993,120 control chromosomes in the GnomAD database, including 335,429 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.85 ( 55678 hom., cov: 33)

Exomes 𝑓: 0.81 ( 279751 hom. )

Consequence

HGF
NM_000601.6 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.41

Publications

20 publications found

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 Gene-Disease associations (from GenCC):

autosomal recessive nonsyndromic hearing loss 39
Inheritance: AR Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
nonsyndromic genetic hearing loss
Inheritance: AR Classification: MODERATE Submitted by: ClinGen
hearing loss, autosomal recessive
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

HGF links:

ENSG00000300407 (HGNC:):

ENSG00000300407 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.96).

BP6

Variant 7-81720892-A-G is Benign according to our data. Variant chr7-81720892-A-G is described in ClinVar as Benign. ClinVar VariationId is 1246790.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.947 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000601.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HGF	NM_000601.6	MANE Select	c.1169-45T>C		intron	N/A	NP_000592.3
	HGF	NM_001010932.3		c.1154-45T>C		intron	N/A	NP_001010932.1	P14210-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
HGF	ENST00000222390.11	TSL:1 MANE Select	c.1169-45T>C	intron	N/A	ENSP00000222390.5	P14210-1
HGF	ENST00000457544.7	TSL:1	c.1154-45T>C	intron	N/A	ENSP00000391238.2	P14210-3
ENSG00000300407	ENST00000771413.1		n.117+20364A>G	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.852

AC:

129635

AN:

152116

Hom.:

55624

Cov.:

show subpopulations

Gnomad AFR

AF:

0.955

Gnomad AMI

AF:

0.735

Gnomad AMR

AF:

0.870

Gnomad ASJ

AF:

0.864

Gnomad EAS

AF:

0.856

Gnomad SAS

AF:

0.873

Gnomad FIN

AF:

0.780

Gnomad MID

AF:

0.918

Gnomad NFE

AF:

0.796

Gnomad OTH

AF:

0.851

GnomAD2 exomes

AF:

0.835

AC:

201034

AN:

240720

AF XY:

0.833

show subpopulations

Gnomad AFR exome

AF:

0.956

Gnomad AMR exome

AF:

0.891

Gnomad ASJ exome

AF:

0.868

Gnomad EAS exome

AF:

0.854

Gnomad FIN exome

AF:

0.791

Gnomad NFE exome

AF:

0.795

Gnomad OTH exome

AF:

0.824

GnomAD4 exome

AF:

0.814

AC:

684405

AN:

840886

Hom.:

279751

Cov.:

AF XY:

0.815

AC XY:

361818

AN XY:

443766

show subpopulations

African (AFR)

AF:

0.957

AC:

20413

AN:

21330

American (AMR)

AF:

0.889

AC:

38504

AN:

43292

Ashkenazi Jewish (ASJ)

AF:

0.867

AC:

19240

AN:

22188

East Asian (EAS)

AF:

0.881

AC:

32380

AN:

36754

South Asian (SAS)

AF:

0.865

AC:

63352

AN:

73210

European-Finnish (FIN)

AF:

0.791

AC:

41687

AN:

52704

Middle Eastern (MID)

AF:

0.867

AC:

3683

AN:

4250

European-Non Finnish (NFE)

AF:

0.790

AC:

432294

AN:

547336

Other (OTH)

AF:

0.825

AC:

32852

AN:

39822

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

6673

13347

20020

26694

33367

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6400

12800

19200

25600

32000

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.852

AC:

129748

AN:

152234

Hom.:

55678

Cov.:

AF XY:

0.852

AC XY:

63369

AN XY:

74414

show subpopulations

African (AFR)

AF:

0.955

AC:

39670

AN:

41560

American (AMR)

AF:

0.870

AC:

13312

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.864

AC:

2998

AN:

3470

East Asian (EAS)

AF:

0.856

AC:

4435

AN:

5182

South Asian (SAS)

AF:

0.873

AC:

4215

AN:

4826

European-Finnish (FIN)

AF:

0.780

AC:

8251

AN:

10580

Middle Eastern (MID)

AF:

0.915

AC:

269

AN:

294

European-Non Finnish (NFE)

AF:

0.796

AC:

54134

AN:

68002

Other (OTH)

AF:

0.849

AC:

1794

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

999

1997

2996

3994

4993

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

892

1784

2676

3568

4460

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.820

Hom.:

7037

Bravo

AF:

0.862

Asia WGS

AF:

0.857

AC:

2982

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

0.046

(source)

DANN

Benign

0.32

PhyloP100

-1.4

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over