dbSNP rs4702: FURIN:c.*1452G>A (chr15-90883330-G-A) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.955

Publications

159 publications found

Variant links:

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]

FURIN links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FURIN	NM_002569.4 link	c.*1452G>A		3_prime_UTR_variant	Exon 16 of 16	ENST00000268171.8	NP_002560.1	P09958A0A024RC70

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FURIN	ENST00000268171.8 link	c.*1452G>A		3_prime_UTR_variant	Exon 16 of 16	1	NM_002569.4	ENSP00000268171.2		P09958

Frequencies

GnomAD3 genomes

AF:

0.643

AC:

97850

AN:

152106

Hom.:

33196

Cov.:

show subpopulations

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.:

AF XY:

0.567

AC XY:

338

AN XY:

596

show subpopulations

African (AFR)

AF:

0.867

AC:

AN:

American (AMR)

AF:

0.417

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.571

AC:

AN:

East Asian (EAS)

AF:

0.378

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.566

AC:

224

AN:

396

Middle Eastern (MID)

AF:

0.750

AC:

AN:

European-Non Finnish (NFE)

AF:

0.536

AC:

256

AN:

478

Other (OTH)

AF:

0.625

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.644

AC:

97968

AN:

152224

Hom.:

33257

Cov.:

AF XY:

0.639

AC XY:

47582

AN XY:

74428

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1707

3414

5121

6828

8535

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

766

1532

2298

3064

3830

<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:

0.573

Hom.:

90789

Bravo

AF:

0.662

Asia WGS

AF:

0.557

AC:

1942

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.46

CADD

Benign

(source)

DANN

Benign

0.87

PhyloP100

0.95

PromoterAI

-0.0083

Neutral

(source)

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