rs6022

Positions:

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_000130.5(F5):c.552G>T(p.Ser184=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.213 in 1,613,178 control chromosomes in the GnomAD database, including 47,929 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. S184S) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.32 ( 10496 hom., cov: 31)

Exomes 𝑓: 0.20 ( 37433 hom. )

Consequence

F5
NM_000130.5 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -0.639

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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.39).

BP6

Variant 1-169560588-C-A is Benign according to our data. Variant chr1-169560588-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 255212.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-169560588-C-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.639 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.634 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.552G>T	p.Ser184=	synonymous_variant	4/25	ENST00000367797.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
F5	ENST00000367797.9 linkuse as main transcript	c.552G>T	p.Ser184=	synonymous_variant	4/25	1	NM_000130.5	P2
F5	ENST00000367796.3 linkuse as main transcript	c.552G>T	p.Ser184=	synonymous_variant	4/25	5		A2

Frequencies

GnomAD3 genomes

AF:

0.322

AC:

48902

AN:

151662

Hom.:

10474

Cov.:

show subpopulations

Gnomad AFR

AF:

0.582

Gnomad AMI

AF:

0.0877

Gnomad AMR

AF:

0.292

Gnomad ASJ

AF:

0.205

Gnomad EAS

AF:

0.653

Gnomad SAS

AF:

0.194

Gnomad FIN

AF:

0.256

Gnomad MID

AF:

0.161

Gnomad NFE

AF:

0.177

Gnomad OTH

AF:

0.300

GnomAD3 exomes

AF:

0.261

AC:

65679

AN:

251384

Hom.:

11764

AF XY:

0.248

AC XY:

33668

AN XY:

135854

show subpopulations

Gnomad AFR exome

AF:

0.589

Gnomad AMR exome

AF:

0.269

Gnomad ASJ exome

AF:

0.211

Gnomad EAS exome

AF:

0.678

Gnomad SAS exome

AF:

0.178

Gnomad FIN exome

AF:

0.255

Gnomad NFE exome

AF:

0.174

Gnomad OTH exome

AF:

0.237

GnomAD4 exome

AF:

0.202

AC:

294949

AN:

1461400

Hom.:

37433

Cov.:

AF XY:

0.199

AC XY:

144917

AN XY:

727034

show subpopulations

Gnomad4 AFR exome

AF:

0.594

Gnomad4 AMR exome

AF:

0.273

Gnomad4 ASJ exome

AF:

0.210

Gnomad4 EAS exome

AF:

0.600

Gnomad4 SAS exome

AF:

0.175

Gnomad4 FIN exome

AF:

0.257

Gnomad4 NFE exome

AF:

0.170

Gnomad4 OTH exome

AF:

0.246

GnomAD4 genome

AF:

0.323

AC:

48970

AN:

151778

Hom.:

10496

Cov.:

AF XY:

0.325

AC XY:

24076

AN XY:

74184

show subpopulations

Gnomad4 AFR

AF:

0.582

Gnomad4 AMR

AF:

0.292

Gnomad4 ASJ

AF:

0.205

Gnomad4 EAS

AF:

0.652

Gnomad4 SAS

AF:

0.193

Gnomad4 FIN

AF:

0.256

Gnomad4 NFE

AF:

0.177

Gnomad4 OTH

AF:

0.305

Alfa

AF:

0.197

Hom.:

5740

Bravo

AF:

0.340

Asia WGS

AF:

0.450

AC:

1563

AN:

3478

EpiCase

AF:

0.173

EpiControl

AF:

0.175

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

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	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

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

not provided

Benign:1

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

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

-0.39

CADD

Benign

0.096

DANN

Benign

0.40

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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