rs6021

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000130.5(F5):c.2301A>G(p.Ser767Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.269 in 1,613,850 control chromosomes in the GnomAD database, including 60,148 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.25 ( 4756 hom., cov: 32)

Exomes 𝑓: 0.27 ( 55392 hom. )

Consequence

F5
NM_000130.5 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: -1.12

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 1-169542789-T-C is Benign according to our data. Variant chr1-169542789-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 255196.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-169542789-T-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-1.12 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.334 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
F5	NM_000130.5 link	c.2301A>G	p.Ser767Ser	synonymous_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.2301A>G	p.Ser767Ser	synonymous_variant	Exon 13 of 25	1	NM_000130.5	ENSP00000356771.3		P12259
F5	ENST00000367796.3 link	c.2316A>G	p.Ser772Ser	synonymous_variant	Exon 13 of 25	5		ENSP00000356770.3		A0A0A0MRJ7

Frequencies

GnomAD3 genomes

AF:

0.245

AC:

37285

AN:

152018

Hom.:

4745

Cov.:

show subpopulations

Gnomad AFR

AF:

0.183

Gnomad AMI

AF:

0.191

Gnomad AMR

AF:

0.341

Gnomad ASJ

AF:

0.169

Gnomad EAS

AF:

0.234

Gnomad SAS

AF:

0.323

Gnomad FIN

AF:

0.210

Gnomad MID

AF:

0.244

Gnomad NFE

AF:

0.266

Gnomad OTH

AF:

0.263

GnomAD3 exomes

AF:

0.278

AC:

69942

AN:

251178

Hom.:

10548

AF XY:

0.278

AC XY:

37777

AN XY:

135746

show subpopulations

Gnomad AFR exome

AF:

0.179

Gnomad AMR exome

AF:

0.415

Gnomad ASJ exome

AF:

0.177

Gnomad EAS exome

AF:

0.221

Gnomad SAS exome

AF:

0.330

Gnomad FIN exome

AF:

0.213

Gnomad NFE exome

AF:

0.268

Gnomad OTH exome

AF:

0.286

GnomAD4 exome

AF:

0.272

AC:

397369

AN:

1461716

Hom.:

55392

Cov.:

AF XY:

0.273

AC XY:

198335

AN XY:

727168

show subpopulations

Gnomad4 AFR exome

AF:

0.180

Gnomad4 AMR exome

AF:

0.409

Gnomad4 ASJ exome

AF:

0.176

Gnomad4 EAS exome

AF:

0.226

Gnomad4 SAS exome

AF:

0.325

Gnomad4 FIN exome

AF:

0.217

Gnomad4 NFE exome

AF:

0.272

Gnomad4 OTH exome

AF:

0.264

GnomAD4 genome

AF:

0.245

AC:

37325

AN:

152134

Hom.:

4756

Cov.:

AF XY:

0.247

AC XY:

18368

AN XY:

74372

show subpopulations

Gnomad4 AFR

AF:

0.183

Gnomad4 AMR

AF:

0.342

Gnomad4 ASJ

AF:

0.169

Gnomad4 EAS

AF:

0.235

Gnomad4 SAS

AF:

0.324

Gnomad4 FIN

AF:

0.210

Gnomad4 NFE

AF:

0.267

Gnomad4 OTH

AF:

0.260

Alfa

AF:

0.254

Hom.:

2178

Bravo

AF:

0.254

Asia WGS

AF:

0.283

AC:

983

AN:

3478

EpiCase

AF:

0.269

EpiControl

AF:

0.270

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 11, 2018

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

- -

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

-0.88

CADD

Benign

0.48

DANN

Benign

0.58

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over