rs4702

Variant names:

• chr15-90883330-G-A
• rs4702
• NM_002569.4:c.*1452G>A

Your query was ambiguous. Multiple possible variants found:

• chr15-90883330-G-A
• chr15-90883330-G-C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_002569.4(FURIN):​c.*1452G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.643 in 153,280 control chromosomes in the GnomAD database, including 33,425 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 0.64 (33257 hom., cov: 34)
  • Exomes 𝑓: 0.55 (168 hom.)
• Consequence: FURIN NM_002569.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.955
• Publications: 160 publications found

Genes affected

FURIN (HGNC:8568): (furin, paired basic amino acid cleaving enzyme) This gene encodes a member of the subtilisin-like proprotein convertase family, which includes proteases that process protein and peptide precursors trafficking through regulated or constitutive branches of the secretory pathway. It encodes a type 1 membrane bound protease that is expressed in many tissues, including neuroendocrine, liver, gut, and brain. The encoded protein undergoes an initial autocatalytic processing event in the ER and then sorts to the trans-Golgi network through endosomes where a second autocatalytic event takes place and the catalytic activity is acquired. Like other members of this convertase family, the product of this gene specifically cleaves substrates at single or paired basic residues. Some of its substrates include proparathyroid hormone, transforming growth factor beta 1 precursor, proalbumin, pro-beta-secretase, membrane type-1 matrix metalloproteinase, beta subunit of pro-nerve growth factor and von Willebrand factor. It is thought to be one of the proteases responsible for the activation of HIV envelope glycoproteins gp160 and gp140, and may play a role in tumor progression. Unlike SARS-CoV and other coronaviruses, the spike protein of SARS-CoV-2 is thought to be uniquely cleaved by this protease. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2020]

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.878 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002569.4. 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
	FURIN	NM_002569.4	MANE Select	c.*1452G>A		3_prime_UTR	Exon 16 of 16	NP_002560.1	P09958
	FURIN	NM_001289823.2		c.*1452G>A		3_prime_UTR	Exon 16 of 16	NP_001276752.1	P09958
	FURIN	NM_001289824.2		c.*1452G>A		3_prime_UTR	Exon 16 of 16	NP_001276753.1	P09958

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FURIN	ENST00000268171.8	TSL:1 MANE Select	c.*1452G>A		3_prime_UTR	Exon 16 of 16	ENSP00000268171.2	P09958
	FURIN	ENST00000853383.1		c.*1452G>A		3_prime_UTR	Exon 17 of 17	ENSP00000523442.1
	FURIN	ENST00000853380.1		c.*1452G>A		3_prime_UTR	Exon 16 of 16	ENSP00000523439.1

Frequencies

GnomAD3 genomes AF: 0.643 AC: 97850 AN: 152106 Hom.: 33196 Cov.: 34

Gnomad AFR AF: 0.885

Gnomad AMI AF: 0.631

Gnomad AMR AF: 0.596

Gnomad ASJ AF: 0.541

Gnomad EAS AF: 0.518

Gnomad SAS AF: 0.502

Gnomad FIN AF: 0.521

Gnomad MID AF: 0.491

Gnomad NFE AF: 0.553

Gnomad OTH AF: 0.589

GnomAD4 exome AF: 0.547 AC: 578 AN: 1056 Hom.: 168 Cov.: 0 AF XY: 0.567 AC XY: 338 AN XY: 596

African (AFR) AF: 0.867 AC: 26 AN: 30

American (AMR) AF: 0.417 AC: 5 AN: 12

Ashkenazi Jewish (ASJ) AF: 0.571 AC: 8 AN: 14

East Asian (EAS) AF: 0.378 AC: 28 AN: 74

South Asian (SAS) AF: 0.00 AC: 0 AN: 4

European-Finnish (FIN) AF: 0.566 AC: 224 AN: 396

Middle Eastern (MID) AF: 0.750 AC: 6 AN: 8

European-Non Finnish (NFE) AF: 0.536 AC: 256 AN: 478

Other (OTH) AF: 0.625 AC: 25 AN: 40

GnomAD4 genome AF: 0.644 AC: 97968 AN: 152224 Hom.: 33257 Cov.: 34 AF XY: 0.639 AC XY: 47582 AN XY: 74428

African (AFR) AF: 0.885 AC: 36789 AN: 41552

American (AMR) AF: 0.597 AC: 9131 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.541 AC: 1880 AN: 3472

East Asian (EAS) AF: 0.517 AC: 2681 AN: 5184

South Asian (SAS) AF: 0.501 AC: 2418 AN: 4828

European-Finnish (FIN) AF: 0.521 AC: 5513 AN: 10572

Middle Eastern (MID) AF: 0.500 AC: 147 AN: 294

European-Non Finnish (NFE) AF: 0.553 AC: 37589 AN: 67992

Other (OTH) AF: 0.589 AC: 1246 AN: 2116

Alfa AF: 0.573 Hom.: 90789

Bravo AF: 0.662

Asia WGS AF: 0.557 AC: 1942 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	13
DANN	Benign	0.87
PhyloP100		0.95
PromoterAI		-0.0083	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs4702;

hg19: chr15-91426560;

COSMIC: COSV51577935;

COSMIC: COSV51577935;