1-169544345-G-T

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.1926C>A(p.Thr642Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0728 in 1,613,708 control chromosomes in the GnomAD database, including 4,834 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.064 ( 450 hom., cov: 32)

Exomes 𝑓: 0.074 ( 4384 hom. )

Consequence

F5
NM_000130.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.262

Publications

15 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=-0.56).

BP6

Variant 1-169544345-G-T is Benign according to our data. Variant chr1-169544345-G-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 255192.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.262 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.106 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000130.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	F5	NM_000130.5	MANE Select	c.1926C>A	p.Thr642Thr	synonymous	Exon 12 of 25	NP_000121.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
F5	ENST00000367797.9	TSL:1 MANE Select	c.1926C>A	p.Thr642Thr	synonymous	Exon 12 of 25	ENSP00000356771.3
F5	ENST00000367796.3	TSL:5	c.1941C>A	p.Thr647Thr	synonymous	Exon 12 of 25	ENSP00000356770.3
F5	ENST00000904428.1		c.1611+5456C>A		intron	N/A	ENSP00000574487.1

Frequencies

GnomAD3 genomes

AF:

0.0640

AC:

9732

AN:

152024

Hom.:

449

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0131

Gnomad AMI

AF:

0.0154

Gnomad AMR

AF:

0.110

Gnomad ASJ

AF:

0.0761

Gnomad EAS

AF:

0.0278

Gnomad SAS

AF:

0.0823

Gnomad FIN

AF:

0.114

Gnomad MID

AF:

0.0854

Gnomad NFE

AF:

0.0780

Gnomad OTH

AF:

0.0742

GnomAD2 exomes

AF:

0.0755

AC:

18959

AN:

251172

AF XY:

0.0771

show subpopulations

Gnomad AFR exome

AF:

0.0110

Gnomad AMR exome

AF:

0.101

Gnomad ASJ exome

AF:

0.0717

Gnomad EAS exome

AF:

0.0290

Gnomad FIN exome

AF:

0.113

Gnomad NFE exome

AF:

0.0750

Gnomad OTH exome

AF:

0.0843

GnomAD4 exome

AF:

0.0737

AC:

107744

AN:

1461566

Hom.:

4384

Cov.:

AF XY:

0.0744

AC XY:

54115

AN XY:

727088

show subpopulations

African (AFR)

AF:

0.0106

AC:

355

AN:

33472

American (AMR)

AF:

0.102

AC:

4546

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.0720

AC:

1881

AN:

26130

East Asian (EAS)

AF:

0.0504

AC:

1999

AN:

39696

South Asian (SAS)

AF:

0.0835

AC:

7200

AN:

86254

European-Finnish (FIN)

AF:

0.112

AC:

5961

AN:

53404

Middle Eastern (MID)

AF:

0.0967

AC:

558

AN:

5768

European-Non Finnish (NFE)

AF:

0.0727

AC:

80834

AN:

1111740

Other (OTH)

AF:

0.0730

AC:

4410

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

5592

11184

16777

22369

27961

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2930

5860

8790

11720

14650

<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:

0.0640

AC:

9731

AN:

152142

Hom.:

450

Cov.:

AF XY:

0.0673

AC XY:

5004

AN XY:

74398

show subpopulations

African (AFR)

AF:

0.0130

AC:

541

AN:

41516

American (AMR)

AF:

0.110

AC:

1680

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.0761

AC:

264

AN:

3470

East Asian (EAS)

AF:

0.0276

AC:

143

AN:

5174

South Asian (SAS)

AF:

0.0826

AC:

398

AN:

4820

European-Finnish (FIN)

AF:

0.114

AC:

1206

AN:

10596

Middle Eastern (MID)

AF:

0.0850

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0780

AC:

5304

AN:

67968

Other (OTH)

AF:

0.0739

AC:

156

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

461

921

1382

1842

2303

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

118

236

354

472

590

<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:

0.0711

Hom.:

1279

Bravo

AF:

0.0595

Asia WGS

AF:

0.0630

AC:

218

AN:

3478

EpiCase

AF:

0.0732

EpiControl

AF:

0.0756

ClinVar

ClinVar submissions as Germline

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Thrombophilia due to activated protein C resistance (2)

Budd-Chiari syndrome (1)

Congenital factor V deficiency (1)

Factor V deficiency (1)

not specified (1)

Thrombophilia due to thrombin defect (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.56

CADD

Benign

5.1

(source)

DANN

Benign

0.61

PhyloP100

0.26

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over