rs9332607

Positions:

chr1-169540995-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.4095C>T(p.Thr1365=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.37 in 1,609,928 control chromosomes in the GnomAD database, including 119,203 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.29 ( 6316 hom., cov: 31)

Exomes 𝑓: 0.38 ( 112887 hom. )

Consequence

F5
NM_000130.5 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts U:1B:8

Conservation

PhyloP100: -3.62

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=-0.87).

BP6

Variant 1-169540995-G-A is Benign according to our data. Variant chr1-169540995-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 255208.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-169540995-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-3.62 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.385 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.4095C>T	p.Thr1365=	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.4095C>T	p.Thr1365=	synonymous_variant	13/25	1	NM_000130.5	P2
F5	ENST00000367796.3 linkuse as main transcript	c.4110C>T	p.Thr1370=	synonymous_variant	13/25	5		A2

Frequencies

GnomAD3 genomes

AF:

0.289

AC:

42938

AN:

148770

Hom.:

6316

Cov.:

show subpopulations

Gnomad AFR

AF:

0.175

Gnomad AMI

AF:

0.509

Gnomad AMR

AF:

0.236

Gnomad ASJ

AF:

0.328

Gnomad EAS

AF:

0.00270

Gnomad SAS

AF:

0.164

Gnomad FIN

AF:

0.343

Gnomad MID

AF:

0.274

Gnomad NFE

AF:

0.389

Gnomad OTH

AF:

0.300

GnomAD3 exomes

AF:

0.294

AC:

73699

AN:

250494

Hom.:

13136

AF XY:

0.299

AC XY:

40442

AN XY:

135430

show subpopulations

Gnomad AFR exome

AF:

0.182

Gnomad AMR exome

AF:

0.172

Gnomad ASJ exome

AF:

0.345

Gnomad EAS exome

AF:

0.000544

Gnomad SAS exome

AF:

0.183

Gnomad FIN exome

AF:

0.368

Gnomad NFE exome

AF:

0.405

Gnomad OTH exome

AF:

0.325

GnomAD4 exome

AF:

0.379

AC:

553539

AN:

1461038

Hom.:

112887

Cov.:

107

AF XY:

0.374

AC XY:

271948

AN XY:

726818

show subpopulations

Gnomad4 AFR exome

AF:

0.181

Gnomad4 AMR exome

AF:

0.182

Gnomad4 ASJ exome

AF:

0.350

Gnomad4 EAS exome

AF:

0.000605

Gnomad4 SAS exome

AF:

0.187

Gnomad4 FIN exome

AF:

0.366

Gnomad4 NFE exome

AF:

0.425

Gnomad4 OTH exome

AF:

0.347

GnomAD4 genome

AF:

0.288

AC:

42938

AN:

148890

Hom.:

6316

Cov.:

AF XY:

0.281

AC XY:

20454

AN XY:

72864

show subpopulations

Gnomad4 AFR

AF:

0.175

Gnomad4 AMR

AF:

0.236

Gnomad4 ASJ

AF:

0.328

Gnomad4 EAS

AF:

0.00290

Gnomad4 SAS

AF:

0.164

Gnomad4 FIN

AF:

0.343

Gnomad4 NFE

AF:

0.389

Gnomad4 OTH

AF:

0.296

Alfa

AF:

0.356

Hom.:

4037

EpiCase

AF:

0.400

EpiControl

AF:

0.398

ClinVar

Significance: Benign/Likely benign

Submissions summary: Uncertain:1Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Uncertain:1Benign:1

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 10, 2018	- -
Uncertain significance, no assertion criteria provided	clinical testing	Department of Pathology and Laboratory Medicine, Sinai Health System	-	multiple AR variants in same gene - keep for nowAllele frequency is common in at least one population database (frequency: 40.459% in gnomAD_Exomes) based on the frequency threshold of 5.0% for this gene.Variant was observed in a homozygous state in population databases more than expected for disease.A synonymous variant not located in a splice region. -

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

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

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

-0.87

CADD

Benign

0.063

DANN

Benign

0.14

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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