rs6017

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

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

The NM_000130.5(F5):c.2235T>C(p.Asn745Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.269 in 1,613,564 control chromosomes in the GnomAD database, including 60,157 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.25 ( 4765 hom., cov: 32)

Exomes 𝑓: 0.27 ( 55392 hom. )

Consequence

F5
NM_000130.5 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: -0.0400

Publications

20 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, ClinGen, Labcorp Genetics (formerly Invitae)
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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 1-169542855-A-G is Benign according to our data. Variant chr1-169542855-A-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 255194.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.04 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.334 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.2235T>C	p.Asn745Asn	synonymous	Exon 13 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.2235T>C	p.Asn745Asn	synonymous	Exon 13 of 25	ENSP00000356771.3	P12259
F5	ENST00000367796.3	TSL:5	c.2250T>C	p.Asn750Asn	synonymous	Exon 13 of 25	ENSP00000356770.3	A0A0A0MRJ7
F5	ENST00000904428.1		c.1611+6946T>C		intron	N/A	ENSP00000574487.1

Frequencies

GnomAD3 genomes

AF:

0.245

AC:

37300

AN:

152050

Hom.:

4753

Cov.:

show subpopulations

Gnomad AFR

AF:

0.183

Gnomad AMI

AF:

0.191

Gnomad AMR

AF:

0.341

Gnomad ASJ

AF:

0.169

Gnomad EAS

AF:

0.235

Gnomad SAS

AF:

0.323

Gnomad FIN

AF:

0.211

Gnomad MID

AF:

0.244

Gnomad NFE

AF:

0.267

Gnomad OTH

AF:

0.261

GnomAD2 exomes

AF:

0.278

AC:

69938

AN:

251162

AF XY:

0.278

show subpopulations

Gnomad AFR exome

AF:

0.178

Gnomad AMR exome

AF:

0.415

Gnomad ASJ exome

AF:

0.177

Gnomad EAS exome

AF:

0.222

Gnomad FIN exome

AF:

0.213

Gnomad NFE exome

AF:

0.268

Gnomad OTH exome

AF:

0.286

GnomAD4 exome

AF:

0.272

AC:

397192

AN:

1461396

Hom.:

55392

Cov.:

AF XY:

0.273

AC XY:

198263

AN XY:

727030

show subpopulations

African (AFR)

AF:

0.180

AC:

6023

AN:

33466

American (AMR)

AF:

0.409

AC:

18274

AN:

44712

Ashkenazi Jewish (ASJ)

AF:

0.176

AC:

4598

AN:

26130

East Asian (EAS)

AF:

0.226

AC:

8984

AN:

39698

South Asian (SAS)

AF:

0.325

AC:

28065

AN:

86240

European-Finnish (FIN)

AF:

0.217

AC:

11592

AN:

53414

Middle Eastern (MID)

AF:

0.276

AC:

1593

AN:

5768

European-Non Finnish (NFE)

AF:

0.272

AC:

302114

AN:

1111594

Other (OTH)

AF:

0.264

AC:

15949

AN:

60374

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.456

Heterozygous variant carriers

17132

34265

51397

68530

85662

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10176

20352

30528

40704

50880

<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:

0.245

AC:

37341

AN:

152168

Hom.:

4765

Cov.:

AF XY:

0.247

AC XY:

18380

AN XY:

74404

show subpopulations

African (AFR)

AF:

0.183

AC:

7599

AN:

41516

American (AMR)

AF:

0.342

AC:

5227

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.169

AC:

585

AN:

3470

East Asian (EAS)

AF:

0.235

AC:

1216

AN:

5176

South Asian (SAS)

AF:

0.324

AC:

1559

AN:

4814

European-Finnish (FIN)

AF:

0.211

AC:

2234

AN:

10594

Middle Eastern (MID)

AF:

0.235

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.267

AC:

18129

AN:

67996

Other (OTH)

AF:

0.260

AC:

549

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1459

2918

4376

5835

7294

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

396

792

1188

1584

1980

<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:

0.235

Hom.:

2396

Bravo

AF:

0.254

Asia WGS

AF:

0.283

AC:

982

AN:

3478

EpiCase

AF:

0.269

EpiControl

AF:

0.270

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (3)

not provided (2)

Thrombophilia due to activated protein C resistance (2)

Budd-Chiari syndrome (1)

Congenital factor V deficiency (1)

Factor V deficiency (1)

Thrombophilia due to thrombin defect (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

4.3

(source)

DANN

Benign

0.31

PhyloP100

-0.040

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

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