Variant chr11-46739206-G-A 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.1726-59G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.481 in 1,613,514 control chromosomes in the GnomAD database, including 197,768 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.38 ( 13994 hom., cov: 31)

Exomes 𝑓: 0.49 ( 183774 hom. )

Consequence

F2
ENST00000311907.10 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3O:1

Conservation

PhyloP100: 0.871

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=-0.73).

BP6

Variant 11-46739206-G-A is Benign according to our data. Variant chr11-46739206-G-A is described in ClinVar as [Benign]. Clinvar id is 143996.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-46739206-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.521 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.1726-59G>A		intron_variant		ENST00000311907.10	NP_000497.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
F2	ENST00000311907.10 linkuse as main transcript	c.1726-59G>A		intron_variant		1	NM_000506.5	ENSP00000308541	P1
F2	ENST00000530231.5 linkuse as main transcript	c.1609-59G>A		intron_variant		5		ENSP00000433907

Frequencies

GnomAD3 genomes

AF:

0.384

AC:

58279

AN:

151840

Hom.:

13989

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0980

Gnomad AMI

AF:

0.567

Gnomad AMR

AF:

0.444

Gnomad ASJ

AF:

0.521

Gnomad EAS

AF:

0.174

Gnomad SAS

AF:

0.364

Gnomad FIN

AF:

0.548

Gnomad MID

AF:

0.449

Gnomad NFE

AF:

0.525

Gnomad OTH

AF:

0.424

GnomAD4 exome

AF:

0.491

AC:

718264

AN:

1461554

Hom.:

183774

Cov.:

AF XY:

0.490

AC XY:

355996

AN XY:

727092

show subpopulations

Gnomad4 AFR exome

AF:

0.0809

Gnomad4 AMR exome

AF:

0.406

Gnomad4 ASJ exome

AF:

0.521

Gnomad4 EAS exome

AF:

0.150

Gnomad4 SAS exome

AF:

0.367

Gnomad4 FIN exome

AF:

0.554

Gnomad4 NFE exome

AF:

0.527

Gnomad4 OTH exome

AF:

0.471

GnomAD4 genome

AF:

0.384

AC:

58281

AN:

151960

Hom.:

13994

Cov.:

AF XY:

0.383

AC XY:

28462

AN XY:

74262

show subpopulations

Gnomad4 AFR

AF:

0.0976

Gnomad4 AMR

AF:

0.443

Gnomad4 ASJ

AF:

0.521

Gnomad4 EAS

AF:

0.173

Gnomad4 SAS

AF:

0.364

Gnomad4 FIN

AF:

0.548

Gnomad4 NFE

AF:

0.525

Gnomad4 OTH

AF:

0.429

Alfa

AF:

0.447

Hom.:

3024

Bravo

AF:

0.365

Asia WGS

AF:

0.285

AC:

996

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3Other:1

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	This variant is associated with the following publications: (PMID: 11434686, 14504098, 16981886, 19652888, 17059428) -

Congenital prothrombin deficiency;C0948008:Ischemic stroke;C3160733:Thrombophilia due to thrombin defect;C3280672:Pregnancy loss, recurrent, susceptibility to, 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Mar 29, 2022

- -

Thrombophilia due to thrombin defect

Other:1

not provided, no classification provided

literature only

GeneReviews

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

7.6

DANN

Benign

0.75

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