chr11-46723439-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000506.5(F2):c.480C>T(p.Pro160Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00759 in 1,614,054 control chromosomes in the GnomAD database, including 786 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.040 ( 413 hom., cov: 32)

Exomes 𝑓: 0.0042 ( 373 hom. )

Consequence

F2
NM_000506.5 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -1.30

Publications

1 publications found

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 Gene-Disease associations (from GenCC):

thrombophilia due to thrombin defect
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, ClinGen
congenital prothrombin deficiency
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), Orphanet

F2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.68).

BP6

Variant 11-46723439-C-T is Benign according to our data. Variant chr11-46723439-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 256316.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.3 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.135 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000506.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	F2	NM_000506.5	MANE Select	c.480C>T	p.Pro160Pro	synonymous	Exon 6 of 14	NP_000497.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
F2	ENST00000311907.10	TSL:1 MANE Select	c.480C>T	p.Pro160Pro	synonymous	Exon 6 of 14	ENSP00000308541.5
F2	ENST00000862106.1		c.480C>T	p.Pro160Pro	synonymous	Exon 6 of 15	ENSP00000532165.1
F2	ENST00000862118.1		c.480C>T	p.Pro160Pro	synonymous	Exon 6 of 14	ENSP00000532177.1

Frequencies

GnomAD3 genomes

AF:

0.0401

AC:

6100

AN:

152096

Hom.:

413

Cov.:

show subpopulations

Gnomad AFR

AF:

0.139

Gnomad AMI

AF:

0.0164

Gnomad AMR

AF:

0.0170

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000353

Gnomad OTH

AF:

0.0282

GnomAD2 exomes

AF:

0.0111

AC:

2794

AN:

251458

AF XY:

0.00804

show subpopulations

Gnomad AFR exome

AF:

0.147

Gnomad AMR exome

AF:

0.00859

Gnomad ASJ exome

AF:

0.00298

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000334

Gnomad OTH exome

AF:

0.00424

GnomAD4 exome

AF:

0.00420

AC:

6144

AN:

1461840

Hom.:

373

Cov.:

AF XY:

0.00362

AC XY:

2633

AN XY:

727228

show subpopulations

African (AFR)

AF:

0.144

AC:

4817

AN:

33478

American (AMR)

AF:

0.00924

AC:

413

AN:

44708

Ashkenazi Jewish (ASJ)

AF:

0.00226

AC:

AN:

26136

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39698

South Asian (SAS)

AF:

0.000394

AC:

AN:

86254

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53404

Middle Eastern (MID)

AF:

0.00555

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000169

AC:

188

AN:

1111998

Other (OTH)

AF:

0.00992

AC:

599

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

366

732

1098

1464

1830

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

148

296

444

592

740

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0401

AC:

6106

AN:

152214

Hom.:

413

Cov.:

AF XY:

0.0382

AC XY:

2847

AN XY:

74436

show subpopulations

African (AFR)

AF:

0.138

AC:

5742

AN:

41514

American (AMR)

AF:

0.0169

AC:

258

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00144

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5162

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000353

AC:

AN:

68008

Other (OTH)

AF:

0.0279

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

270

540

811

1081

1351

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

180

240

300

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0186

Hom.:

126

Bravo

AF:

0.0472

Asia WGS

AF:

0.00808

AC:

AN:

3478

EpiCase

AF:

0.000436

EpiControl

AF:

0.000474

ClinVar

ClinVar submissions as Germline

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Congenital prothrombin deficiency (2)

not provided (2)

not specified (1)

Thrombophilia due to thrombin defect (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

0.26

(source)

DANN

Benign

0.73

PhyloP100

-1.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over