rs6028

Positions:

chr1-169582444-T-C

Variant summary

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

The NM_000130.5(F5):c.237A>G(p.Gln79Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.271 in 1,507,572 control chromosomes in the GnomAD database, including 58,939 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.23 ( 4921 hom., cov: 33)

Exomes 𝑓: 0.28 ( 54018 hom. )

Consequence

F5
NM_000130.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.610

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=-0.61).

BP6

Variant 1-169582444-T-C is Benign according to our data. Variant chr1-169582444-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 255197.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-169582444-T-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.61 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.344 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.237A>G	p.Gln79Gln	synonymous_variant	2/25	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.237A>G	p.Gln79Gln	synonymous_variant	2/25	1	NM_000130.5	ENSP00000356771.3		P12259
F5	ENST00000367796.3 linkuse as main transcript	c.237A>G	p.Gln79Gln	synonymous_variant	2/25	5		ENSP00000356770.3		A0A0A0MRJ7

Frequencies

GnomAD3 genomes

AF:

0.231

AC:

35185

AN:

152090

Hom.:

4909

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0677

Gnomad AMI

AF:

0.153

Gnomad AMR

AF:

0.322

Gnomad ASJ

AF:

0.263

Gnomad EAS

AF:

0.219

Gnomad SAS

AF:

0.357

Gnomad FIN

AF:

0.353

Gnomad MID

AF:

0.239

Gnomad NFE

AF:

0.283

Gnomad OTH

AF:

0.248

GnomAD3 exomes

AF:

0.291

AC:

70058

AN:

240928

Hom.:

11171

AF XY:

0.291

AC XY:

38041

AN XY:

130554

show subpopulations

Gnomad AFR exome

AF:

0.0623

Gnomad AMR exome

AF:

0.431

Gnomad ASJ exome

AF:

0.259

Gnomad EAS exome

AF:

0.191

Gnomad SAS exome

AF:

0.337

Gnomad FIN exome

AF:

0.343

Gnomad NFE exome

AF:

0.280

Gnomad OTH exome

AF:

0.270

GnomAD4 exome

AF:

0.275

AC:

373211

AN:

1355362

Hom.:

54018

Cov.:

AF XY:

0.278

AC XY:

188256

AN XY:

678108

show subpopulations

Gnomad4 AFR exome

AF:

0.0545

Gnomad4 AMR exome

AF:

0.415

Gnomad4 ASJ exome

AF:

0.258

Gnomad4 EAS exome

AF:

0.255

Gnomad4 SAS exome

AF:

0.335

Gnomad4 FIN exome

AF:

0.339

Gnomad4 NFE exome

AF:

0.271

Gnomad4 OTH exome

AF:

0.254

GnomAD4 genome

AF:

0.231

AC:

35201

AN:

152210

Hom.:

4921

Cov.:

AF XY:

0.237

AC XY:

17667

AN XY:

74400

show subpopulations

Gnomad4 AFR

AF:

0.0675

Gnomad4 AMR

AF:

0.323

Gnomad4 ASJ

AF:

0.263

Gnomad4 EAS

AF:

0.219

Gnomad4 SAS

AF:

0.358

Gnomad4 FIN

AF:

0.353

Gnomad4 NFE

AF:

0.283

Gnomad4 OTH

AF:

0.244

Alfa

AF:

0.265

Hom.:

4951

Bravo

AF:

0.223

Asia WGS

AF:

0.273

AC:

946

AN:

3468

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	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
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	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 04, 2021	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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

-0.61

CADD

Benign

5.5

DANN

Benign

0.53

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