rs6019

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.319G>C(p.Asp107His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0676 in 1,612,870 control chromosomes in the GnomAD database, including 7,268 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.13 ( 2680 hom., cov: 32)

Exomes 𝑓: 0.061 ( 4588 hom. )

Consequence

F5
NM_000130.5 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.813

Publications

33 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=0.0040112734).

BP6

Variant 1-169572275-C-G is Benign according to our data. Variant chr1-169572275-C-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 255203.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.341 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
F5	NM_000130.5 link	c.319G>C	p.Asp107His	missense_variant	Exon 3 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.319G>C	p.Asp107His	missense_variant	Exon 3 of 25	1	NM_000130.5	ENSP00000356771.3
F5	ENST00000367796.3 link	c.319G>C	p.Asp107His	missense_variant	Exon 3 of 25	5		ENSP00000356770.3

Frequencies

GnomAD3 genomes

AF:

0.131

AC:

19982

AN:

151980

Hom.:

2676

Cov.:

show subpopulations

Gnomad AFR

AF:

0.347

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.0683

Gnomad ASJ

AF:

0.0455

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.0137

Gnomad FIN

AF:

0.0234

Gnomad MID

AF:

0.0669

Gnomad NFE

AF:

0.0574

Gnomad OTH

AF:

0.0989

GnomAD2 exomes

AF:

0.0623

AC:

15617

AN:

250658

AF XY:

0.0554

show subpopulations

Gnomad AFR exome

AF:

0.356

Gnomad AMR exome

AF:

0.0488

Gnomad ASJ exome

AF:

0.0534

Gnomad EAS exome

AF:

0.000436

Gnomad FIN exome

AF:

0.0255

Gnomad NFE exome

AF:

0.0554

Gnomad OTH exome

AF:

0.0641

GnomAD4 exome

AF:

0.0610

AC:

89113

AN:

1460772

Hom.:

4588

Cov.:

AF XY:

0.0585

AC XY:

42500

AN XY:

726700

show subpopulations

African (AFR)

AF:

0.357

AC:

11931

AN:

33412

American (AMR)

AF:

0.0524

AC:

2341

AN:

44652

Ashkenazi Jewish (ASJ)

AF:

0.0541

AC:

1412

AN:

26106

East Asian (EAS)

AF:

0.000176

AC:

AN:

39666

South Asian (SAS)

AF:

0.0128

AC:

1107

AN:

86238

European-Finnish (FIN)

AF:

0.0283

AC:

1507

AN:

53186

Middle Eastern (MID)

AF:

0.0792

AC:

456

AN:

5760

European-Non Finnish (NFE)

AF:

0.0594

AC:

66005

AN:

1111432

Other (OTH)

AF:

0.0721

AC:

4347

AN:

60320

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

3941

7881

11822

15762

19703

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2598

5196

7794

10392

12990

<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:

0.131

AC:

19990

AN:

152098

Hom.:

2680

Cov.:

AF XY:

0.124

AC XY:

9195

AN XY:

74372

show subpopulations

African (AFR)

AF:

0.346

AC:

14342

AN:

41428

American (AMR)

AF:

0.0681

AC:

1041

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.0455

AC:

158

AN:

3472

East Asian (EAS)

AF:

0.000386

AC:

AN:

5176

South Asian (SAS)

AF:

0.0135

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.0234

AC:

248

AN:

10604

Middle Eastern (MID)

AF:

0.0719

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0574

AC:

3905

AN:

67990

Other (OTH)

AF:

0.0979

AC:

207

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

765

1529

2294

3058

3823

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

188

376

564

752

940

<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:

0.0676

Hom.:

451

Bravo

AF:

0.145

TwinsUK

AF:

0.0609

AC:

226

ALSPAC

AF:

0.0573

AC:

221

ESP6500AA

AF:

0.342

AC:

1506

ESP6500EA

AF:

0.0548

AC:

471

ExAC

AF:

0.0685

AC:

8319

Asia WGS

AF:

0.0280

AC:

AN:

3478

EpiCase

AF:

0.0575

EpiControl

AF:

0.0570

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

- -

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: 23662219, 12651267, 19020903, 22044617) -

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

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. -

Factor V deficiency

Benign:1

Apr 27, 2017

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Thrombophilia due to thrombin defect

Benign:1

Apr 27, 2017

Illumina Laboratory Services, Illumina

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

0.16

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.18

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Uncertain

0.60

D;T

Eigen

Benign

-0.14

Eigen_PC

Benign

-0.021

FATHMM_MKL

Benign

0.29

LIST_S2

Benign

0.31

T;T

MetaRNN

Benign

0.0040

T;T

MetaSVM

Uncertain

0.59

MutationAssessor

Uncertain

2.1

M;.

PhyloP100

0.81

PrimateAI

Benign

0.29

PROVEAN

Uncertain

-3.8

D;D

REVEL

Uncertain

0.33

Sift

Benign

0.14

T;T

Sift4G

Benign

0.13

T;T

Polyphen

0.063

B;.

Vest4

0.11

MPC

0.13

ClinPred

0.019

GERP RS

3.2

Varity_R

0.16

gMVP

0.62

Mutation Taster

=297/3

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