dbSNP rs6227: FURIN:c.*124C>T (chr15-90882002-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002569.4(FURIN):c.*124C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.288 in 709,594 control chromosomes in the GnomAD database, including 31,744 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 0.28 ( 6233 hom., cov: 33)

Exomes 𝑓: 0.29 ( 25511 hom. )

Consequence

FURIN
NM_002569.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.53

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 made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.323 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FURIN	NM_002569.4 link	c.*124C>T		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.*124C>T		3_prime_UTR_variant	Exon 16 of 16	1	NM_002569.4	ENSP00000268171.2		P09958

Frequencies

GnomAD3 genomes

AF:

0.280

AC:

42576

AN:

151976

Hom.:

6223

Cov.:

show subpopulations

Gnomad AFR

AF:

0.253

Gnomad AMI

AF:

0.286

Gnomad AMR

AF:

0.240

Gnomad ASJ

AF:

0.348

Gnomad EAS

AF:

0.0691

Gnomad SAS

AF:

0.222

Gnomad FIN

AF:

0.251

Gnomad MID

AF:

0.280

Gnomad NFE

AF:

0.327

Gnomad OTH

AF:

0.283

GnomAD4 exome

AF:

0.290

AC:

161870

AN:

557500

Hom.:

25511

Cov.:

AF XY:

0.289

AC XY:

83974

AN XY:

290128

show subpopulations

Gnomad4 AFR exome

AF:

0.253

Gnomad4 AMR exome

AF:

0.182

Gnomad4 ASJ exome

AF:

0.344

Gnomad4 EAS exome

AF:

0.0752

Gnomad4 SAS exome

AF:

0.237

Gnomad4 FIN exome

AF:

0.263

Gnomad4 NFE exome

AF:

0.326

Gnomad4 OTH exome

AF:

0.286

GnomAD4 genome

AF:

0.280

AC:

42609

AN:

152094

Hom.:

6233

Cov.:

AF XY:

0.274

AC XY:

20406

AN XY:

74346

show subpopulations

Gnomad4 AFR

AF:

0.254

Gnomad4 AMR

AF:

0.240

Gnomad4 ASJ

AF:

0.348

Gnomad4 EAS

AF:

0.0696

Gnomad4 SAS

AF:

0.221

Gnomad4 FIN

AF:

0.251

Gnomad4 NFE

AF:

0.327

Gnomad4 OTH

AF:

0.283

Alfa

AF:

0.318

Hom.:

4869

Bravo

AF:

0.277

Asia WGS

AF:

0.172

AC:

600

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

DANN

Benign

0.76

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