Genetic Variant HGFAC:c.1102+79C>T (chr4-3445429-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001528.4(HGFAC):c.1102+79C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.226 in 975,980 control chromosomes in the GnomAD database, including 27,609 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.19 ( 3484 hom., cov: 33)

Exomes 𝑓: 0.23 ( 24125 hom. )

Consequence

HGFAC
NM_001528.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.61

Publications

15 publications found

Variant links:

Genes affected

HGFAC (HGNC:4894): (HGF activator) This gene encodes a member of the peptidase S1 protein family. The encoded protein is first synthesized as an inactive single-chain precursor before being activated to a heterodimeric form by endoproteolytic processing. It acts as serine protease that converts hepatocyte growth factor to the active form. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]

HGFAC links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.436 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001528.4. 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
	HGFAC	NM_001528.4	MANE Select	c.1102+79C>T		intron	N/A	NP_001519.1	Q04756
	HGFAC	NM_001297439.2		c.1102+79C>T		intron	N/A	NP_001284368.1	D6RAR4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HGFAC	ENST00000382774.8	TSL:1 MANE Select	c.1102+79C>T		intron	N/A	ENSP00000372224.4	Q04756
HGFAC	ENST00000511533.1	TSL:1	c.1102+79C>T		intron	N/A	ENSP00000421801.1	D6RAR4
HGFAC	ENST00000882382.1		c.1086C>T	p.Ser362Ser	synonymous	Exon 10 of 15	ENSP00000552441.1

Frequencies

GnomAD3 genomes

AF:

0.188

AC:

28551

AN:

151944

Hom.:

3483

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0452

Gnomad AMI

AF:

0.218

Gnomad AMR

AF:

0.220

Gnomad ASJ

AF:

0.236

Gnomad EAS

AF:

0.452

Gnomad SAS

AF:

0.195

Gnomad FIN

AF:

0.253

Gnomad MID

AF:

0.157

Gnomad NFE

AF:

0.234

Gnomad OTH

AF:

0.207

GnomAD4 exome

AF:

0.233

AC:

192012

AN:

823918

Hom.:

24125

Cov.:

AF XY:

0.231

AC XY:

98644

AN XY:

426352

show subpopulations

African (AFR)

AF:

0.0408

AC:

840

AN:

20602

American (AMR)

AF:

0.247

AC:

8568

AN:

34700

Ashkenazi Jewish (ASJ)

AF:

0.222

AC:

4722

AN:

21240

East Asian (EAS)

AF:

0.429

AC:

14180

AN:

33062

South Asian (SAS)

AF:

0.177

AC:

11925

AN:

67522

European-Finnish (FIN)

AF:

0.266

AC:

12302

AN:

46280

Middle Eastern (MID)

AF:

0.187

AC:

646

AN:

3456

European-Non Finnish (NFE)

AF:

0.232

AC:

129668

AN:

558194

Other (OTH)

AF:

0.236

AC:

9161

AN:

38862

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

7878

15756

23634

31512

39390

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3112

6224

9336

12448

15560

<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:

0.188

AC:

28547

AN:

152062

Hom.:

3484

Cov.:

AF XY:

0.191

AC XY:

14177

AN XY:

74314

show subpopulations

African (AFR)

AF:

0.0451

AC:

1873

AN:

41524

American (AMR)

AF:

0.220

AC:

3366

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.236

AC:

819

AN:

3472

East Asian (EAS)

AF:

0.451

AC:

2324

AN:

5150

South Asian (SAS)

AF:

0.195

AC:

938

AN:

4798

European-Finnish (FIN)

AF:

0.253

AC:

2678

AN:

10584

Middle Eastern (MID)

AF:

0.159

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.234

AC:

15864

AN:

67938

Other (OTH)

AF:

0.209

AC:

441

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1180

2361

3541

4722

5902

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

318

636

954

1272

1590

<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:

0.221

Hom.:

8128

Bravo

AF:

0.183

Asia WGS

AF:

0.331

AC:

1151

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

6.6

(source)

DANN

Benign

0.73

PhyloP100

-3.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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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