rs6016

Positions:

chr1-169542882-G-A

Variant summary

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

The NM_000130.5(F5):c.2208C>T(p.Ile736=) 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 1,613,338 control chromosomes in the GnomAD database, including 60,137 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 ( 55381 hom. )

Consequence

F5
NM_000130.5 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: 0.212

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=-0.71).

BP6

Variant 1-169542882-G-A is Benign according to our data. Variant chr1-169542882-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 255193.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-169542882-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.212 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/exons	MANE	UniProt
F5	NM_000130.5 linkuse as main transcript	c.2208C>T	p.Ile736=	synonymous_variant	13/25	ENST00000367797.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
F5	ENST00000367797.9 linkuse as main transcript	c.2208C>T	p.Ile736=	synonymous_variant	13/25	1	NM_000130.5	P2
F5	ENST00000367796.3 linkuse as main transcript	c.2223C>T	p.Ile741=	synonymous_variant	13/25	5		A2

Frequencies

GnomAD3 genomes

AF:

0.245

AC:

37284

AN:

152002

Hom.:

4744

Cov.:

show subpopulations

Gnomad AFR

AF:

0.183

Gnomad AMI

AF:

0.192

Gnomad AMR

AF:

0.341

Gnomad ASJ

AF:

0.168

Gnomad EAS

AF:

0.235

Gnomad SAS

AF:

0.323

Gnomad FIN

AF:

0.211

Gnomad MID

AF:

0.241

Gnomad NFE

AF:

0.267

Gnomad OTH

AF:

0.262

GnomAD3 exomes

AF:

0.278

AC:

69914

AN:

251090

Hom.:

10546

AF XY:

0.278

AC XY:

37765

AN XY:

135700

show subpopulations

Gnomad AFR exome

AF:

0.178

Gnomad AMR exome

AF:

0.415

Gnomad ASJ exome

AF:

0.177

Gnomad EAS exome

AF:

0.222

Gnomad SAS exome

AF:

0.330

Gnomad FIN exome

AF:

0.213

Gnomad NFE exome

AF:

0.268

Gnomad OTH exome

AF:

0.285

GnomAD4 exome

AF:

0.272

AC:

397076

AN:

1461218

Hom.:

55381

Cov.:

AF XY:

0.273

AC XY:

198201

AN XY:

726928

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:

152120

Hom.:

4756

Cov.:

AF XY:

0.247

AC XY:

18365

AN XY:

74364

show subpopulations

Gnomad4 AFR

AF:

0.183

Gnomad4 AMR

AF:

0.342

Gnomad4 ASJ

AF:

0.168

Gnomad4 EAS

AF:

0.235

Gnomad4 SAS

AF:

0.324

Gnomad4 FIN

AF:

0.211

Gnomad4 NFE

AF:

0.267

Gnomad4 OTH

AF:

0.260

Alfa

AF:

0.265

Hom.:

10862

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:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

Thrombophilia due to activated protein C resistance

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -
Likely benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -

Congenital factor V deficiency

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Budd-Chiari syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

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

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 11, 2018

- -

Thrombophilia due to thrombin defect

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.71

CADD

Benign

1.4

DANN

Benign

0.63

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

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