rs6035

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.1242A>G(p.Lys414Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0839 in 1,613,148 control chromosomes in the GnomAD database, including 5,881 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.086 ( 606 hom., cov: 32)

Exomes 𝑓: 0.084 ( 5275 hom. )

Consequence

F5
NM_000130.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.122

Publications

23 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=-0.84).

BP6

Variant 1-169552611-T-C is Benign according to our data. Variant chr1-169552611-T-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 255189.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.122 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0919 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
F5	NM_000130.5 link	c.1242A>G	p.Lys414Lys	synonymous_variant	Exon 8 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.1242A>G	p.Lys414Lys	synonymous_variant	Exon 8 of 25	1	NM_000130.5	ENSP00000356771.3
F5	ENST00000367796.3 link	c.1242A>G	p.Lys414Lys	synonymous_variant	Exon 8 of 25	5		ENSP00000356770.3

Frequencies

GnomAD3 genomes

AF:

0.0863

AC:

13124

AN:

152140

Hom.:

607

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0945

Gnomad AMI

AF:

0.0592

Gnomad AMR

AF:

0.0955

Gnomad ASJ

AF:

0.157

Gnomad EAS

AF:

0.0604

Gnomad SAS

AF:

0.0942

Gnomad FIN

AF:

0.0573

Gnomad MID

AF:

0.0886

Gnomad NFE

AF:

0.0817

Gnomad OTH

AF:

0.0900

GnomAD2 exomes

AF:

0.0877

AC:

22041

AN:

251372

AF XY:

0.0875

show subpopulations

Gnomad AFR exome

AF:

0.0939

Gnomad AMR exome

AF:

0.101

Gnomad ASJ exome

AF:

0.160

Gnomad EAS exome

AF:

0.0636

Gnomad FIN exome

AF:

0.0576

Gnomad NFE exome

AF:

0.0826

Gnomad OTH exome

AF:

0.0856

GnomAD4 exome

AF:

0.0836

AC:

122170

AN:

1460890

Hom.:

5275

Cov.:

AF XY:

0.0844

AC XY:

61319

AN XY:

726772

show subpopulations

African (AFR)

AF:

0.0945

AC:

3160

AN:

33454

American (AMR)

AF:

0.102

AC:

4565

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.151

AC:

3944

AN:

26120

East Asian (EAS)

AF:

0.0595

AC:

2359

AN:

39622

South Asian (SAS)

AF:

0.101

AC:

8711

AN:

86230

European-Finnish (FIN)

AF:

0.0581

AC:

3101

AN:

53414

Middle Eastern (MID)

AF:

0.0798

AC:

457

AN:

5730

European-Non Finnish (NFE)

AF:

0.0815

AC:

90553

AN:

1111252

Other (OTH)

AF:

0.0882

AC:

5320

AN:

60348

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

5263

10526

15788

21051

26314

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3398

6796

10194

13592

16990

<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:

0.0862

AC:

13127

AN:

152258

Hom.:

606

Cov.:

AF XY:

0.0837

AC XY:

6235

AN XY:

74458

show subpopulations

African (AFR)

AF:

0.0944

AC:

3921

AN:

41532

American (AMR)

AF:

0.0952

AC:

1456

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.157

AC:

544

AN:

3468

East Asian (EAS)

AF:

0.0607

AC:

315

AN:

5186

South Asian (SAS)

AF:

0.0939

AC:

453

AN:

4826

European-Finnish (FIN)

AF:

0.0573

AC:

608

AN:

10610

Middle Eastern (MID)

AF:

0.0918

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0817

AC:

5556

AN:

68018

Other (OTH)

AF:

0.0914

AC:

193

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

627

1254

1880

2507

3134

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

154

308

462

616

770

<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:

0.0882

Hom.:

992

Bravo

AF:

0.0877

Asia WGS

AF:

0.103

AC:

358

AN:

3476

EpiCase

AF:

0.0922

EpiControl

AF:

0.0906

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

Feb 01, 2017

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nov 12, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 27884173, 16542711, 20981092) -

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

BayesDel_noAF

Benign

-0.84

CADD

Benign

5.4

(source)

DANN

Benign

0.65

PhyloP100

0.12

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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