Variant rs4702 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
FURIN	NM_002569.4 linkuse as main transcript	c.*1452G>A		3_prime_UTR_variant	16/16	ENST00000268171.8	NP_002560.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FURIN	ENST00000268171.8 linkuse as main transcript	c.*1452G>A		3_prime_UTR_variant	16/16	1	NM_002569.4	ENSP00000268171	P1

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

Gnomad4 AFR exome

AF:

0.867

Gnomad4 AMR exome

AF:

0.417

Gnomad4 ASJ exome

AF:

0.571

Gnomad4 EAS exome

AF:

0.378

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.566

Gnomad4 NFE exome

AF:

0.536

Gnomad4 OTH exome

AF:

0.625

GnomAD4 genome

AF:

0.644

AC:

97968

AN:

152224

Hom.:

33257

Cov.:

AF XY:

0.639

AC XY:

47582

AN XY:

74428

show subpopulations

Gnomad4 AFR

AF:

0.885

Gnomad4 AMR

AF:

0.597

Gnomad4 ASJ

AF:

0.541

Gnomad4 EAS

AF:

0.517

Gnomad4 SAS

AF:

0.501

Gnomad4 FIN

AF:

0.521

Gnomad4 NFE

AF:

0.553

Gnomad4 OTH

AF:

0.589

Alfa

AF:

0.562

Hom.:

32308

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

DANN

Benign

0.87

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over