rs6022

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_000130.5(F5):c.552G>T(p.Ser184Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.213 in 1,613,178 control chromosomes in the GnomAD database, including 47,929 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. S184S) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.32 ( 10496 hom., cov: 31)

Exomes 𝑓: 0.20 ( 37433 hom. )

Consequence

F5
NM_000130.5 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -0.639

Publications

29 publications found

Variant links:

Genes affected

F5 (HGNC:3542): (coagulation factor V) This gene encodes an essential cofactor of the blood coagulation cascade. This factor circulates in plasma, and is converted to the active form by the release of the activation peptide by thrombin during coagulation. This generates a heavy chain and a light chain which are held together by calcium ions. The activated protein is a cofactor that participates with activated coagulation factor X to activate prothrombin to thrombin. Defects in this gene result in either an autosomal recessive hemorrhagic diathesis or an autosomal dominant form of thrombophilia, which is known as activated protein C resistance. [provided by RefSeq, Oct 2008]

F5 Gene-Disease associations (from GenCC):

thrombophilia due to activated protein C resistance
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), ClinGen
congenital factor V deficiency
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Orphanet, Labcorp Genetics (formerly Invitae)
East Texas bleeding disorder
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

F5 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.39).

BP6

Variant 1-169560588-C-A is Benign according to our data. Variant chr1-169560588-C-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 255212.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.639 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.634 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000130.5. 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
	F5	NM_000130.5	MANE Select	c.552G>T	p.Ser184Ser	synonymous	Exon 4 of 25	NP_000121.2	P12259

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
F5	ENST00000367797.9	TSL:1 MANE Select	c.552G>T	p.Ser184Ser	synonymous	Exon 4 of 25	ENSP00000356771.3	P12259
F5	ENST00000367796.3	TSL:5	c.552G>T	p.Ser184Ser	synonymous	Exon 4 of 25	ENSP00000356770.3	A0A0A0MRJ7
F5	ENST00000904428.1		c.552G>T	p.Ser184Ser	synonymous	Exon 4 of 21	ENSP00000574487.1

Frequencies

GnomAD3 genomes

AF:

0.322

AC:

48902

AN:

151662

Hom.:

10474

Cov.:

show subpopulations

Gnomad AFR

AF:

0.582

Gnomad AMI

AF:

0.0877

Gnomad AMR

AF:

0.292

Gnomad ASJ

AF:

0.205

Gnomad EAS

AF:

0.653

Gnomad SAS

AF:

0.194

Gnomad FIN

AF:

0.256

Gnomad MID

AF:

0.161

Gnomad NFE

AF:

0.177

Gnomad OTH

AF:

0.300

GnomAD2 exomes

AF:

0.261

AC:

65679

AN:

251384

AF XY:

0.248

show subpopulations

Gnomad AFR exome

AF:

0.589

Gnomad AMR exome

AF:

0.269

Gnomad ASJ exome

AF:

0.211

Gnomad EAS exome

AF:

0.678

Gnomad FIN exome

AF:

0.255

Gnomad NFE exome

AF:

0.174

Gnomad OTH exome

AF:

0.237

GnomAD4 exome

AF:

0.202

AC:

294949

AN:

1461400

Hom.:

37433

Cov.:

AF XY:

0.199

AC XY:

144917

AN XY:

727034

show subpopulations

African (AFR)

AF:

0.594

AC:

19863

AN:

33438

American (AMR)

AF:

0.273

AC:

12218

AN:

44694

Ashkenazi Jewish (ASJ)

AF:

0.210

AC:

5484

AN:

26120

East Asian (EAS)

AF:

0.600

AC:

23826

AN:

39698

South Asian (SAS)

AF:

0.175

AC:

15055

AN:

86256

European-Finnish (FIN)

AF:

0.257

AC:

13722

AN:

53418

Middle Eastern (MID)

AF:

0.215

AC:

1238

AN:

5768

European-Non Finnish (NFE)

AF:

0.170

AC:

188674

AN:

1111644

Other (OTH)

AF:

0.246

AC:

14869

AN:

60364

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

12860

25719

38579

51438

64298

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7032

14064

21096

28128

35160

<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:

0.323

AC:

48970

AN:

151778

Hom.:

10496

Cov.:

AF XY:

0.325

AC XY:

24076

AN XY:

74184

show subpopulations

African (AFR)

AF:

0.582

AC:

24080

AN:

41362

American (AMR)

AF:

0.292

AC:

4447

AN:

15246

Ashkenazi Jewish (ASJ)

AF:

0.205

AC:

710

AN:

3462

East Asian (EAS)

AF:

0.652

AC:

3338

AN:

5118

South Asian (SAS)

AF:

0.193

AC:

932

AN:

4818

European-Finnish (FIN)

AF:

0.256

AC:

2696

AN:

10542

Middle Eastern (MID)

AF:

0.167

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.177

AC:

11994

AN:

67914

Other (OTH)

AF:

0.305

AC:

644

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1422

2843

4265

5686

7108

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

442

884

1326

1768

2210

<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:

0.209

Hom.:

8249

Bravo

AF:

0.340

Asia WGS

AF:

0.450

AC:

1563

AN:

3478

EpiCase

AF:

0.173

EpiControl

AF:

0.175

ClinVar

ClinVar submissions as Germline

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Thrombophilia due to activated protein C resistance (2)

Budd-Chiari syndrome (1)

Congenital factor V deficiency (1)

Factor V deficiency (1)

not provided (1)

not specified (1)

Thrombophilia due to thrombin defect (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.39

CADD

Benign

0.096

(source)

DANN

Benign

0.40

PhyloP100

-0.64

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=79/21

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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