rs6015

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.1380C>T(p.Asn460Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0734 in 1,612,416 control chromosomes in the GnomAD database, including 4,941 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.065 ( 459 hom., cov: 31)

Exomes 𝑓: 0.074 ( 4482 hom. )

Consequence

F5
NM_000130.5 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 2.36

Publications

15 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: ClinGen, Labcorp Genetics (formerly Invitae), Genomics England PanelApp
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=-0.57).

BP6

Variant 1-169550656-G-A is Benign according to our data. Variant chr1-169550656-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 255190.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=2.36 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.106 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
F5	NM_000130.5 link	c.1380C>T	p.Asn460Asn	synonymous_variant	Exon 9 of 25	ENST00000367797.9	NP_000121.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
F5	ENST00000367797.9 link	c.1380C>T	p.Asn460Asn	synonymous_variant	Exon 9 of 25	1	NM_000130.5	ENSP00000356771.3
F5	ENST00000367796.3 link	c.1380C>T	p.Asn460Asn	synonymous_variant	Exon 9 of 25	5		ENSP00000356770.3

Frequencies

GnomAD3 genomes

AF:

0.0647

AC:

9833

AN:

152078

Hom.:

458

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0134

Gnomad AMI

AF:

0.0154

Gnomad AMR

AF:

0.111

Gnomad ASJ

AF:

0.0764

Gnomad EAS

AF:

0.0272

Gnomad SAS

AF:

0.0831

Gnomad FIN

AF:

0.116

Gnomad MID

AF:

0.0886

Gnomad NFE

AF:

0.0788

Gnomad OTH

AF:

0.0757

GnomAD2 exomes

AF:

0.0755

AC:

18979

AN:

251288

AF XY:

0.0772

show subpopulations

Gnomad AFR exome

AF:

0.0113

Gnomad AMR exome

AF:

0.0971

Gnomad ASJ exome

AF:

0.0716

Gnomad EAS exome

AF:

0.0287

Gnomad FIN exome

AF:

0.115

Gnomad NFE exome

AF:

0.0759

Gnomad OTH exome

AF:

0.0855

GnomAD4 exome

AF:

0.0743

AC:

108484

AN:

1460220

Hom.:

4482

Cov.:

AF XY:

0.0750

AC XY:

54470

AN XY:

726534

show subpopulations

African (AFR)

AF:

0.0108

AC:

360

AN:

33468

American (AMR)

AF:

0.0985

AC:

4403

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.0718

AC:

1875

AN:

26118

East Asian (EAS)

AF:

0.0504

AC:

1999

AN:

39682

South Asian (SAS)

AF:

0.0826

AC:

7122

AN:

86236

European-Finnish (FIN)

AF:

0.114

AC:

6062

AN:

53394

Middle Eastern (MID)

AF:

0.0973

AC:

561

AN:

5764

European-Non Finnish (NFE)

AF:

0.0735

AC:

81656

AN:

1110506

Other (OTH)

AF:

0.0737

AC:

4446

AN:

60332

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.459

Heterozygous variant carriers

4884

9767

14651

19534

24418

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2952

5904

8856

11808

14760

<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:

0.0646

AC:

9831

AN:

152196

Hom.:

459

Cov.:

AF XY:

0.0679

AC XY:

5052

AN XY:

74408

show subpopulations

African (AFR)

AF:

0.0133

AC:

553

AN:

41542

American (AMR)

AF:

0.111

AC:

1690

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.0764

AC:

265

AN:

3470

East Asian (EAS)

AF:

0.0271

AC:

140

AN:

5166

South Asian (SAS)

AF:

0.0832

AC:

401

AN:

4822

European-Finnish (FIN)

AF:

0.116

AC:

1223

AN:

10574

Middle Eastern (MID)

AF:

0.0884

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0788

AC:

5360

AN:

68020

Other (OTH)

AF:

0.0754

AC:

159

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

454

908

1362

1816

2270

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

240

360

480

600

<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:

0.0743

Hom.:

722

Bravo

AF:

0.0597

Asia WGS

AF:

0.0630

AC:

219

AN:

3478

EpiCase

AF:

0.0736

EpiControl

AF:

0.0768

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Sep 19, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Thrombophilia due to activated protein C resistance

Benign:2

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Congenital factor V deficiency

Benign:1

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Budd-Chiari syndrome

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Factor V deficiency

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Thrombophilia due to thrombin defect

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.57

CADD

Benign

8.3

(source)

DANN

Benign

0.74

PhyloP100

2.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=99/1

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over