Variant chr1-94539598-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_001993.5(F3):c.212+659C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0115 in 152,278 control chromosomes in the GnomAD database, including 48 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 0.011 ( 48 hom., cov: 32)

Consequence

F3
NM_001993.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.363

Variant links:

Genes affected

F3 (HGNC:3541): (coagulation factor III, tissue factor) This gene encodes coagulation factor III which is a cell surface glycoprotein. This factor enables cells to initiate the blood coagulation cascades, and it functions as the high-affinity receptor for the coagulation factor VII. The resulting complex provides a catalytic event that is responsible for initiation of the coagulation protease cascades by specific limited proteolysis. Unlike the other cofactors of these protease cascades, which circulate as nonfunctional precursors, this factor is a potent initiator that is fully functional when expressed on cell surfaces, for example, on monocytes. There are 3 distinct domains of this factor: extracellular, transmembrane, and cytoplasmic. Platelets and monocytes have been shown to express this coagulation factor under procoagulatory and proinflammatory stimuli, and a major role in HIV-associated coagulopathy has been described. Platelet-dependent monocyte expression of coagulation factor III has been described to be associated with Coronavirus Disease 2019 (COVID-19) severity and mortality. This protein is the only one in the coagulation pathway for which a congenital deficiency has not been described. Alternate splicing results in multiple transcript variants.[provided by RefSeq, Aug 2020]

F3 links:

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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).

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0115 (1745/152278) while in subpopulation AFR AF= 0.0398 (1654/41550). AF 95% confidence interval is 0.0382. There are 48 homozygotes in gnomad4. There are 792 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 48 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
F3	NM_001993.5 linkuse as main transcript	c.212+659C>G		intron_variant		ENST00000334047.12
F3	NM_001178096.2 linkuse as main transcript	c.212+659C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris	UniProt
F3	ENST00000334047.12 linkuse as main transcript	c.212+659C>G	intron_variant	1	NM_001993.5	P1	P13726-1
F3	ENST00000370207.4 linkuse as main transcript	c.212+659C>G	intron_variant	1			P13726-2
F3	ENST00000480356.1 linkuse as main transcript	n.830+659C>G	intron_variant, non_coding_transcript_variant	5

Frequencies

GnomAD3 genomes

AF:

0.0115

AC:

1744

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0399

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00393

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000162

Gnomad OTH

AF:

0.00816

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.0115

AC:

1745

AN:

152278

Hom.:

Cov.:

AF XY:

0.0106

AC XY:

792

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.0398

Gnomad4 AMR

AF:

0.00392

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000162

Gnomad4 OTH

AF:

0.00807

Alfa

AF:

0.000212

Hom.:

Bravo

AF:

0.0134

Asia WGS

AF:

0.00289

AC:

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

1.5

DANN

Benign

0.49

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