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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
HGFAC	NM_001528.4 link	c.1102+79C>T	intron_variant	Intron 9 of 13	ENST00000382774.8	NP_001519.1	Q04756
HGFAC	NM_001297439.2 link	c.1102+79C>T	intron_variant	Intron 9 of 14		NP_001284368.1	Q04756D6RAR4
HGFAC	XM_047450155.1 link	c.751+79C>T	intron_variant	Intron 9 of 13		XP_047306111.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
HGFAC	ENST00000382774.8 link	c.1102+79C>T	intron_variant	Intron 9 of 13	1	NM_001528.4	ENSP00000372224.4	Q04756
HGFAC	ENST00000511533.1 link	c.1102+79C>T	intron_variant	Intron 9 of 14	1		ENSP00000421801.1	D6RAR4
HGFAC	ENST00000509689.5 link	n.545C>T	non_coding_transcript_exon_variant	Exon 4 of 9	5

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 v4.3

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over