Variant rs3136435 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000311907.10(F2):c.316+36G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0833 in 1,612,902 control chromosomes in the GnomAD database, including 8,822 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.15 ( 2948 hom., cov: 32)

Exomes 𝑓: 0.077 ( 5874 hom. )

Consequence

F2
ENST00000311907.10 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.0760

Variant links:

Genes affected

F2 (HGNC:3535): (coagulation factor II, thrombin) This gene encodes the prothrombin protein (also known as coagulation factor II). This protein is proteolytically cleaved in multiple steps to form the activated serine protease thrombin. The activated thrombin enzyme plays an important role in thrombosis and hemostasis by converting fibrinogen to fibrin during blood clot formation, by stimulating platelet aggregation, and by activating additional coagulation factors. Thrombin also plays a role in cell proliferation, tissue repair, and angiogenesis as well as maintaining vascular integrity during development and postnatal life. Peptides derived from the C-terminus of this protein have antimicrobial activity against E. coli and P. aeruginosa. Mutations in this gene lead to various forms of thrombosis and dysprothrombinemia. Rapid increases in cytokine levels following coronavirus infections can dysregulate the coagulation cascade and produce thrombosis, compromised blood supply, and organ failure. [provided by RefSeq, May 2020]

F2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 11-46720876-G-A is Benign according to our data. Variant chr11-46720876-G-A is described in ClinVar as [Benign]. Clinvar id is 1290658.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.351 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
F2	NM_000506.5 linkuse as main transcript	c.316+36G>A		intron_variant		ENST00000311907.10	NP_000497.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris
F2	ENST00000311907.10 linkuse as main transcript	c.316+36G>A	intron_variant	1	NM_000506.5	ENSP00000308541	P1
F2	ENST00000442468.1 linkuse as main transcript	c.286+36G>A	intron_variant	3		ENSP00000387413
F2	ENST00000530231.5 linkuse as main transcript	c.316+36G>A	intron_variant	5		ENSP00000433907

Frequencies

GnomAD3 genomes

AF:

0.148

AC:

22541

AN:

151996

Hom.:

2937

Cov.:

show subpopulations

Gnomad AFR

AF:

0.356

Gnomad AMI

AF:

0.0954

Gnomad AMR

AF:

0.0769

Gnomad ASJ

AF:

0.0664

Gnomad EAS

AF:

0.101

Gnomad SAS

AF:

0.0561

Gnomad FIN

AF:

0.0473

Gnomad MID

AF:

0.111

Gnomad NFE

AF:

0.0696

Gnomad OTH

AF:

0.133

GnomAD3 exomes

AF:

0.0842

AC:

21029

AN:

249896

Hom.:

1593

AF XY:

0.0789

AC XY:

10660

AN XY:

135154

show subpopulations

Gnomad AFR exome

AF:

0.361

Gnomad AMR exome

AF:

0.0441

Gnomad ASJ exome

AF:

0.0640

Gnomad EAS exome

AF:

0.0959

Gnomad SAS exome

AF:

0.0614

Gnomad FIN exome

AF:

0.0456

Gnomad NFE exome

AF:

0.0705

Gnomad OTH exome

AF:

0.0760

GnomAD4 exome

AF:

0.0765

AC:

111787

AN:

1460788

Hom.:

5874

Cov.:

AF XY:

0.0752

AC XY:

54668

AN XY:

726662

show subpopulations

Gnomad4 AFR exome

AF:

0.369

Gnomad4 AMR exome

AF:

0.0477

Gnomad4 ASJ exome

AF:

0.0664

Gnomad4 EAS exome

AF:

0.0870

Gnomad4 SAS exome

AF:

0.0653

Gnomad4 FIN exome

AF:

0.0467

Gnomad4 NFE exome

AF:

0.0703

Gnomad4 OTH exome

AF:

0.0890

GnomAD4 genome

AF:

0.148

AC:

22582

AN:

152114

Hom.:

2948

Cov.:

AF XY:

0.145

AC XY:

10799

AN XY:

74376

show subpopulations

Gnomad4 AFR

AF:

0.356

Gnomad4 AMR

AF:

0.0768

Gnomad4 ASJ

AF:

0.0664

Gnomad4 EAS

AF:

0.101

Gnomad4 SAS

AF:

0.0555

Gnomad4 FIN

AF:

0.0473

Gnomad4 NFE

AF:

0.0696

Gnomad4 OTH

AF:

0.131

Alfa

AF:

0.0861

Hom.:

942

Bravo

AF:

0.159

Asia WGS

AF:

0.101

AC:

352

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 11, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

2.7

DANN

Benign

0.59

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.1

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over