rs4690098

Positions:

• chr4-3445429-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000382774.8(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 ENST00000382774.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.61

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]

ACMG classification

Verdict is Benign. Variant got -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	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HGFAC	NM_001528.4	c.1102+79C>T		intron_variant		ENST00000382774.8	NP_001519.1
HGFAC	NM_001297439.2	c.1102+79C>T		intron_variant			NP_001284368.1
HGFAC	XM_047450155.1	c.751+79C>T		intron_variant			XP_047306111.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HGFAC	ENST00000382774.8	c.1102+79C>T		intron_variant		1	NM_001528.4	ENSP00000372224	P2
HGFAC	ENST00000511533.1	c.1102+79C>T		intron_variant		1		ENSP00000421801	A2
HGFAC	ENST00000509689.5	n.545C>T		non_coding_transcript_exon_variant	4/9	5

Frequencies

GnomAD3 genomes AF: 0.188 AC: 28551 AN: 151944 Hom.: 3483 Cov.: 33

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.: 11 AF XY: 0.231 AC XY: 98644 AN XY: 426352

Gnomad4 AFR exome AF: 0.0408

Gnomad4 AMR exome AF: 0.247

Gnomad4 ASJ exome AF: 0.222

Gnomad4 EAS exome AF: 0.429

Gnomad4 SAS exome AF: 0.177

Gnomad4 FIN exome AF: 0.266

Gnomad4 NFE exome AF: 0.232

Gnomad4 OTH exome AF: 0.236

GnomAD4 genome AF: 0.188 AC: 28547 AN: 152062 Hom.: 3484 Cov.: 33 AF XY: 0.191 AC XY: 14177 AN XY: 74314

Gnomad4 AFR AF: 0.0451

Gnomad4 AMR AF: 0.220

Gnomad4 ASJ AF: 0.236

Gnomad4 EAS AF: 0.451

Gnomad4 SAS AF: 0.195

Gnomad4 FIN AF: 0.253

Gnomad4 NFE AF: 0.234

Gnomad4 OTH AF: 0.209

Alfa AF: 0.223 Hom.: 5324

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
DANN	Benign	0.73
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs4690098; hg19: chr4-3447156; COSMIC: COSV66976869; COSMIC: COSV66976869;