rs6027

Variant names:

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.6665A>G(p.Asp2222Gly) variant causes a missense change. The variant allele was found at a frequency of 0.0594 in 1,612,978 control chromosomes in the GnomAD database, including 3,361 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.054 ( 350 hom., cov: 32)

Exomes 𝑓: 0.060 ( 3011 hom. )

Consequence

F5
NM_000130.5 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 6.84

Publications

49 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=0.009426534).

BP6

Variant 1-169514323-T-C is Benign according to our data. Variant chr1-169514323-T-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 255215.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0959 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
F5	NM_000130.5 link	c.6665A>G	p.Asp2222Gly	missense_variant	Exon 25 of 25	ENST00000367797.9	NP_000121.2	P12259

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
F5	ENST00000367797.9 link	c.6665A>G	p.Asp2222Gly	missense_variant	Exon 25 of 25	1	NM_000130.5	ENSP00000356771.3	P12259
F5	ENST00000367796.3 link	c.6680A>G	p.Asp2227Gly	missense_variant	Exon 25 of 25	5		ENSP00000356770.3	A0A0A0MRJ7
F5	ENST00000495481.1 link	n.439A>G		non_coding_transcript_exon_variant	Exon 2 of 2	2

Frequencies

GnomAD3 genomes

AF:

0.0540

AC:

8202

AN:

152012

Hom.:

349

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0108

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.100

Gnomad ASJ

AF:

0.0750

Gnomad EAS

AF:

0.0298

Gnomad SAS

AF:

0.0725

Gnomad FIN

AF:

0.0853

Gnomad MID

AF:

0.0823

Gnomad NFE

AF:

0.0647

Gnomad OTH

AF:

0.0637

GnomAD2 exomes

AF:

0.0641

AC:

16084

AN:

251060

AF XY:

0.0649

show subpopulations

Gnomad AFR exome

AF:

0.00888

Gnomad AMR exome

AF:

0.0938

Gnomad ASJ exome

AF:

0.0696

Gnomad EAS exome

AF:

0.0296

Gnomad FIN exome

AF:

0.0863

Gnomad NFE exome

AF:

0.0611

Gnomad OTH exome

AF:

0.0673

GnomAD4 exome

AF:

0.0600

AC:

87631

AN:

1460848

Hom.:

3011

Cov.:

AF XY:

0.0608

AC XY:

44201

AN XY:

726756

show subpopulations

African (AFR)

AF:

0.00843

AC:

282

AN:

33434

American (AMR)

AF:

0.0940

AC:

4196

AN:

44616

Ashkenazi Jewish (ASJ)

AF:

0.0690

AC:

1800

AN:

26090

East Asian (EAS)

AF:

0.0594

AC:

2356

AN:

39670

South Asian (SAS)

AF:

0.0730

AC:

6296

AN:

86232

European-Finnish (FIN)

AF:

0.0841

AC:

4490

AN:

53400

Middle Eastern (MID)

AF:

0.0688

AC:

396

AN:

5760

European-Non Finnish (NFE)

AF:

0.0579

AC:

64303

AN:

1111324

Other (OTH)

AF:

0.0582

AC:

3512

AN:

60322

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

4159

8318

12476

16635

20794

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2326

4652

6978

9304

11630

<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:

0.0539

AC:

8202

AN:

152130

Hom.:

350

Cov.:

AF XY:

0.0564

AC XY:

4198

AN XY:

74382

show subpopulations

African (AFR)

AF:

0.0108

AC:

447

AN:

41516

American (AMR)

AF:

0.100

AC:

1527

AN:

15256

Ashkenazi Jewish (ASJ)

AF:

0.0750

AC:

260

AN:

3466

East Asian (EAS)

AF:

0.0298

AC:

154

AN:

5164

South Asian (SAS)

AF:

0.0723

AC:

349

AN:

4826

European-Finnish (FIN)

AF:

0.0853

AC:

905

AN:

10606

Middle Eastern (MID)

AF:

0.0816

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0648

AC:

4402

AN:

67982

Other (OTH)

AF:

0.0630

AC:

133

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

382

764

1146

1528

1910

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

200

300

400

500

<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:

0.0596

Hom.:

1581

Bravo

AF:

0.0499

TwinsUK

AF:

0.0515

AC:

191

ALSPAC

AF:

0.0516

AC:

199

ESP6500AA

AF:

0.00953

AC:

ESP6500EA

AF:

0.0617

AC:

531

ExAC

AF:

0.0606

AC:

7362

Asia WGS

AF:

0.0610

AC:

212

AN:

3478

EpiCase

AF:

0.0614

EpiControl

AF:

0.0625

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

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: 33103541, 31399523, 22044617, 14656739, 14695293, 25896652, 20694279) -

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

- -

Thrombophilia due to activated protein C resistance

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.35

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.14

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.38

T;T

Eigen

Uncertain

0.59

Eigen_PC

Uncertain

0.57

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.78

T;T

MetaRNN

Benign

0.0094

T;T

MetaSVM

Uncertain

0.25

MutationAssessor

Uncertain

2.3

M;.

PhyloP100

6.8

PrimateAI

Uncertain

0.55

PROVEAN

Pathogenic

-5.7

D;D

REVEL

Uncertain

0.61

Sift

Uncertain

0.0040

D;D

Sift4G

Uncertain

0.0090

D;D

Polyphen

1.0

D;.

Vest4

0.41

MPC

0.40

ClinPred

0.012

GERP RS

4.9

Varity_R

0.82

gMVP

0.79

Mutation Taster

=49/51

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