rs1800595

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000130.5(F5):c.3980A>G(p.His1327Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0522 in 1,538,076 control chromosomes in the GnomAD database, including 3,267 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.052 ( 245 hom., cov: 29)

Exomes 𝑓: 0.052 ( 3022 hom. )

Consequence

F5
NM_000130.5 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6O:1

Conservation

PhyloP100: 1.72

Publications

101 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0023017824).

BP6

Variant 1-169541110-T-C is Benign according to our data. Variant chr1-169541110-T-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 37345.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.093 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
F5	NM_000130.5 link	c.3980A>G	p.His1327Arg	missense_variant	Exon 13 of 25	ENST00000367797.9	NP_000121.2	P12259

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
F5	ENST00000367797.9 link	c.3980A>G	p.His1327Arg	missense_variant	Exon 13 of 25	1	NM_000130.5	ENSP00000356771.3		P12259
F5	ENST00000367796.3 link	c.3995A>G	p.His1332Arg	missense_variant	Exon 13 of 25	5		ENSP00000356770.3		A0A0A0MRJ7

Frequencies

GnomAD3 genomes

AF:

0.0515

AC:

7727

AN:

149898

Hom.:

244

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0103

Gnomad AMI

AF:

0.00331

Gnomad AMR

AF:

0.0971

Gnomad ASJ

AF:

0.0718

Gnomad EAS

AF:

0.0266

Gnomad SAS

AF:

0.0662

Gnomad FIN

AF:

0.0766

Gnomad MID

AF:

0.0728

Gnomad NFE

AF:

0.0626

Gnomad OTH

AF:

0.0632

GnomAD2 exomes

AF:

0.0567

AC:

13974

AN:

246626

AF XY:

0.0574

show subpopulations

Gnomad AFR exome

AF:

0.00747

Gnomad AMR exome

AF:

0.0751

Gnomad ASJ exome

AF:

0.0623

Gnomad EAS exome

AF:

0.0281

Gnomad FIN exome

AF:

0.0799

Gnomad NFE exome

AF:

0.0563

Gnomad OTH exome

AF:

0.0644

GnomAD4 exome

AF:

0.0523

AC:

72579

AN:

1388066

Hom.:

3022

Cov.:

118

AF XY:

0.0537

AC XY:

36986

AN XY:

689074

show subpopulations

African (AFR)

AF:

0.00810

AC:

262

AN:

32364

American (AMR)

AF:

0.0799

AC:

3215

AN:

40256

Ashkenazi Jewish (ASJ)

AF:

0.0651

AC:

1628

AN:

25016

East Asian (EAS)

AF:

0.0580

AC:

2158

AN:

37212

South Asian (SAS)

AF:

0.0692

AC:

5342

AN:

77232

European-Finnish (FIN)

AF:

0.0820

AC:

4163

AN:

50754

Middle Eastern (MID)

AF:

0.0835

AC:

463

AN:

5544

European-Non Finnish (NFE)

AF:

0.0492

AC:

52247

AN:

1062544

Other (OTH)

AF:

0.0543

AC:

3101

AN:

57144

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.451

Heterozygous variant carriers

5026

10051

15077

20102

25128

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1778

3556

5334

7112

8890

<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:

0.0515

AC:

7729

AN:

150010

Hom.:

245

Cov.:

AF XY:

0.0534

AC XY:

3911

AN XY:

73246

show subpopulations

African (AFR)

AF:

0.0103

AC:

421

AN:

40914

American (AMR)

AF:

0.0971

AC:

1458

AN:

15012

Ashkenazi Jewish (ASJ)

AF:

0.0718

AC:

248

AN:

3452

East Asian (EAS)

AF:

0.0267

AC:

135

AN:

5062

South Asian (SAS)

AF:

0.0663

AC:

311

AN:

4692

European-Finnish (FIN)

AF:

0.0766

AC:

788

AN:

10282

Middle Eastern (MID)

AF:

0.0714

AC:

AN:

280

European-Non Finnish (NFE)

AF:

0.0626

AC:

4214

AN:

67330

Other (OTH)

AF:

0.0630

AC:

131

AN:

2080

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

310

619

929

1238

1548

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

188

282

376

470

<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:

0.0457

Hom.:

102

TwinsUK

AF:

0.0539

AC:

200

ALSPAC

AF:

0.0529

AC:

204

ESP6500AA

AF:

0.0102

AC:

ESP6500EA

AF:

0.0633

AC:

544

ExAC

AF:

0.0611

AC:

7409

Asia WGS

AF:

0.0520

AC:

180

AN:

3456

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

May 04, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 33103541, 24175756, 22023244, 9375735, 19652888) -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Thrombophilia due to activated protein C resistance

Benign:1Other:1

GeneReviews

Significance:not provided

Review Status:no classification provided

Collection Method:literature only

- -

Apr 27, 2017

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -

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

- -

Factor V deficiency

Benign:1

May 28, 2019

Mendelics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.71

CADD

Benign

(source)

DANN

Benign

0.59

DEOGEN2

Benign

0.042

T;T

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.075

LIST_S2

Benign

0.61

T;T

MetaRNN

Benign

0.0023

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.81

L;.

PhyloP100

1.7

PrimateAI

Benign

0.19

PROVEAN

Benign

-0.73

N;N

REVEL

Benign

0.025

Sift

Benign

0.054

T;T

Sift4G

Benign

0.16

T;T

Polyphen

0.15

B;.

Vest4

0.15

MPC

0.11

ClinPred

0.0033

GERP RS

2.2

Varity_R

0.044

gMVP

0.41

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

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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