rs4690098

Variant names:

• chr4-3445429-C-A
• rs4690098
• NM_001528.4:c.1102+79C>A

Your query was ambiguous. Multiple possible variants found:

• chr4-3445429-C-A
• chr4-3445429-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001528.4(HGFAC):​c.1102+79C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000121 in 825,016 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000012 (0 hom.)
• Consequence: HGFAC NM_001528.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.61
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000121 AC: 1 AN: 825016 Hom.: 0 Cov.: 11 AF XY: 0.00 AC XY: 0 AN XY: 426886

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 20602

American (AMR) AF: 0.00 AC: 0 AN: 34712

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21242

East Asian (EAS) AF: 0.00 AC: 0 AN: 33070

South Asian (SAS) AF: 0.00 AC: 0 AN: 67540

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46308

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3456

European-Non Finnish (NFE) AF: 0.00000179 AC: 1 AN: 559192

Other (OTH) AF: 0.00 AC: 0 AN: 38894

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.8
DANN	Benign	0.75
PhyloP100		-3.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Other links and lift over

dbSNP: rs4690098; hg19: chr4-3447156;