rs1800594

Positions:

Variant summary

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

The NM_000130.5(F5):c.3804T>C(p.Ser1268Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.334 in 1,581,322 control chromosomes in the GnomAD database, including 90,328 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.34 ( 7075 hom., cov: 26)

Exomes 𝑓: 0.33 ( 83253 hom. )

Consequence

F5
NM_000130.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.35

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=-0.96).

BP6

Variant 1-169541286-A-G is Benign according to our data. Variant chr1-169541286-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 255204.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-169541286-A-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-1.35 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.465 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
F5	NM_000130.5 linkuse as main transcript	c.3804T>C	p.Ser1268Ser	synonymous_variant	13/25	ENST00000367797.9	NP_000121.2	P12259

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
F5	ENST00000367797.9 linkuse as main transcript	c.3804T>C	p.Ser1268Ser	synonymous_variant	13/25	1	NM_000130.5	ENSP00000356771.3		P12259
F5	ENST00000367796.3 linkuse as main transcript	c.3819T>C	p.Ser1273Ser	synonymous_variant	13/25	5		ENSP00000356770.3		A0A0A0MRJ7

Frequencies

GnomAD3 genomes

AF:

0.339

AC:

44420

AN:

130954

Hom.:

7063

Cov.:

show subpopulations

Gnomad AFR

AF:

0.237

Gnomad AMI

AF:

0.242

Gnomad AMR

AF:

0.474

Gnomad ASJ

AF:

0.271

Gnomad EAS

AF:

0.315

Gnomad SAS

AF:

0.433

Gnomad FIN

AF:

0.347

Gnomad MID

AF:

0.409

Gnomad NFE

AF:

0.361

Gnomad OTH

AF:

0.369

GnomAD3 exomes

AF:

0.343

AC:

85016

AN:

247572

Hom.:

15828

AF XY:

0.344

AC XY:

46101

AN XY:

133984

show subpopulations

Gnomad AFR exome

AF:

0.188

Gnomad AMR exome

AF:

0.514

Gnomad ASJ exome

AF:

0.244

Gnomad EAS exome

AF:

0.254

Gnomad SAS exome

AF:

0.403

Gnomad FIN exome

AF:

0.298

Gnomad NFE exome

AF:

0.330

Gnomad OTH exome

AF:

0.360

GnomAD4 exome

AF:

0.334

AC:

483672

AN:

1450290

Hom.:

83253

Cov.:

AF XY:

0.335

AC XY:

241822

AN XY:

721128

show subpopulations

Gnomad4 AFR exome

AF:

0.192

Gnomad4 AMR exome

AF:

0.507

Gnomad4 ASJ exome

AF:

0.246

Gnomad4 EAS exome

AF:

0.287

Gnomad4 SAS exome

AF:

0.399

Gnomad4 FIN exome

AF:

0.300

Gnomad4 NFE exome

AF:

0.331

Gnomad4 OTH exome

AF:

0.326

GnomAD4 genome

AF:

0.339

AC:

44460

AN:

131032

Hom.:

7075

Cov.:

AF XY:

0.344

AC XY:

21950

AN XY:

63882

show subpopulations

Gnomad4 AFR

AF:

0.237

Gnomad4 AMR

AF:

0.474

Gnomad4 ASJ

AF:

0.271

Gnomad4 EAS

AF:

0.316

Gnomad4 SAS

AF:

0.434

Gnomad4 FIN

AF:

0.347

Gnomad4 NFE

AF:

0.361

Gnomad4 OTH

AF:

0.368

Alfa

AF:

0.318

Hom.:

3268

Asia WGS

AF:

0.331

AC:

1129

AN:

3416

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

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

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 11, 2018	- -

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

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Budd-Chiari syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 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 13, 2018

Thrombophilia due to thrombin defect

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

0.059

DANN

Benign

0.29

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