1-169529596-T-C

Position:

chr1-169529596-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000130.5(F5):c.5419+12A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.936 in 1,610,466 control chromosomes in the GnomAD database, including 705,925 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.93 ( 65297 hom., cov: 31)

Exomes 𝑓: 0.94 ( 640628 hom. )

Consequence

F5
NM_000130.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.348

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.68).

BP6

Variant 1-169529596-T-C is Benign according to our data. Variant chr1-169529596-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 255211.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-169529596-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 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.5419+12A>G		intron_variant		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.5419+12A>G		intron_variant		1	NM_000130.5	ENSP00000356771.3		P12259
F5	ENST00000367796.3 linkuse as main transcript	c.5434+12A>G		intron_variant		5		ENSP00000356770.3		A0A0A0MRJ7

Frequencies

GnomAD3 genomes

AF:

0.926

AC:

140819

AN:

152078

Hom.:

65245

Cov.:

show subpopulations

Gnomad AFR

AF:

0.895

Gnomad AMI

AF:

0.893

Gnomad AMR

AF:

0.950

Gnomad ASJ

AF:

0.876

Gnomad EAS

AF:

0.999

Gnomad SAS

AF:

0.934

Gnomad FIN

AF:

0.950

Gnomad MID

AF:

0.851

Gnomad NFE

AF:

0.933

Gnomad OTH

AF:

0.925

GnomAD3 exomes

AF:

0.937

AC:

234759

AN:

250570

Hom.:

110130

AF XY:

0.935

AC XY:

126629

AN XY:

135458

show subpopulations

Gnomad AFR exome

AF:

0.895

Gnomad AMR exome

AF:

0.968

Gnomad ASJ exome

AF:

0.881

Gnomad EAS exome

AF:

0.999

Gnomad SAS exome

AF:

0.930

Gnomad FIN exome

AF:

0.949

Gnomad NFE exome

AF:

0.928

Gnomad OTH exome

AF:

0.937

GnomAD4 exome

AF:

0.937

AC:

1366487

AN:

1458270

Hom.:

640628

Cov.:

AF XY:

0.936

AC XY:

679390

AN XY:

725644

show subpopulations

Gnomad4 AFR exome

AF:

0.895

Gnomad4 AMR exome

AF:

0.966

Gnomad4 ASJ exome

AF:

0.882

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

0.926

Gnomad4 FIN exome

AF:

0.949

Gnomad4 NFE exome

AF:

0.937

Gnomad4 OTH exome

AF:

0.933

GnomAD4 genome

AF:

0.926

AC:

140928

AN:

152196

Hom.:

65297

Cov.:

AF XY:

0.928

AC XY:

69010

AN XY:

74400

show subpopulations

Gnomad4 AFR

AF:

0.894

Gnomad4 AMR

AF:

0.950

Gnomad4 ASJ

AF:

0.876

Gnomad4 EAS

AF:

0.999

Gnomad4 SAS

AF:

0.934

Gnomad4 FIN

AF:

0.950

Gnomad4 NFE

AF:

0.933

Gnomad4 OTH

AF:

0.926

Alfa

AF:

0.923

Hom.:

12316

Bravo

AF:

0.924

Asia WGS

AF:

0.970

AC:

3373

AN:

3476

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, 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	-	- -

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

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

-0.68

CADD

Benign

DANN

Benign

0.74

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