chr1-169542801-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000130.5(F5):c.2289A>G(p.Glu763Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0611 in 1,614,122 control chromosomes in the GnomAD database, including 3,539 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.055 ( 357 hom., cov: 32)

Exomes 𝑓: 0.062 ( 3182 hom. )

Consequence

F5
NM_000130.5 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: -0.153

Publications

12 publications found

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 Gene-Disease associations (from GenCC):

thrombophilia due to activated protein C resistance
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), Genomics England PanelApp
congenital factor V deficiency
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Orphanet, Labcorp Genetics (formerly Invitae)
East Texas bleeding disorder
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

F5 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 1-169542801-T-C is Benign according to our data. Variant chr1-169542801-T-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 255195.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.153 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.098 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
F5	NM_000130.5 link	c.2289A>G	p.Glu763Glu	synonymous_variant	Exon 13 of 25	ENST00000367797.9	NP_000121.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
F5	ENST00000367797.9 link	c.2289A>G	p.Glu763Glu	synonymous_variant	Exon 13 of 25	1	NM_000130.5	ENSP00000356771.3
F5	ENST00000367796.3 link	c.2304A>G	p.Glu768Glu	synonymous_variant	Exon 13 of 25	5		ENSP00000356770.3

Frequencies

GnomAD3 genomes

AF:

0.0549

AC:

8362

AN:

152182

Hom.:

356

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0111

Gnomad AMI

AF:

0.00329

Gnomad AMR

AF:

0.102

Gnomad ASJ

AF:

0.0752

Gnomad EAS

AF:

0.0300

Gnomad SAS

AF:

0.0735

Gnomad FIN

AF:

0.0836

Gnomad MID

AF:

0.0823

Gnomad NFE

AF:

0.0664

Gnomad OTH

AF:

0.0670

GnomAD2 exomes

AF:

0.0654

AC:

16420

AN:

251174

AF XY:

0.0662

show subpopulations

Gnomad AFR exome

AF:

0.00898

Gnomad AMR exome

AF:

0.0957

Gnomad ASJ exome

AF:

0.0699

Gnomad EAS exome

AF:

0.0303

Gnomad FIN exome

AF:

0.0855

Gnomad NFE exome

AF:

0.0628

Gnomad OTH exome

AF:

0.0740

GnomAD4 exome

AF:

0.0618

AC:

90301

AN:

1461822

Hom.:

3182

Cov.:

AF XY:

0.0626

AC XY:

45531

AN XY:

727218

show subpopulations

African (AFR)

AF:

0.00908

AC:

304

AN:

33472

American (AMR)

AF:

0.0962

AC:

4301

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.0705

AC:

1843

AN:

26134

East Asian (EAS)

AF:

0.0599

AC:

2380

AN:

39700

South Asian (SAS)

AF:

0.0738

AC:

6364

AN:

86256

European-Finnish (FIN)

AF:

0.0835

AC:

4458

AN:

53418

Middle Eastern (MID)

AF:

0.0891

AC:

514

AN:

5768

European-Non Finnish (NFE)

AF:

0.0597

AC:

66399

AN:

1111958

Other (OTH)

AF:

0.0619

AC:

3738

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

5250

10500

15751

21001

26251

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2416

4832

7248

9664

12080

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0549

AC:

8364

AN:

152300

Hom.:

357

Cov.:

AF XY:

0.0572

AC XY:

4262

AN XY:

74468

show subpopulations

African (AFR)

AF:

0.0110

AC:

459

AN:

41574

American (AMR)

AF:

0.102

AC:

1562

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.0752

AC:

261

AN:

3472

East Asian (EAS)

AF:

0.0301

AC:

156

AN:

5186

South Asian (SAS)

AF:

0.0736

AC:

355

AN:

4824

European-Finnish (FIN)

AF:

0.0836

AC:

887

AN:

10616

Middle Eastern (MID)

AF:

0.0816

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0664

AC:

4516

AN:

68022

Other (OTH)

AF:

0.0668

AC:

141

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

388

776

1163

1551

1939

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

102

204

306

408

510

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0629

Hom.:

251

Bravo

AF:

0.0514

Asia WGS

AF:

0.0630

AC:

218

AN:

3478

EpiCase

AF:

0.0628

EpiControl

AF:

0.0635

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Sep 19, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Thrombophilia due to activated protein C resistance

Benign:2

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Congenital factor V deficiency

Benign:1

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Budd-Chiari syndrome

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Thrombophilia due to thrombin defect

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.52

(source)

DANN

Benign

0.46

PhyloP100

-0.15

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over