chr1-169542789-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.2301A>G(p.Ser767Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.269 in 1,613,850 control chromosomes in the GnomAD database, including 60,148 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.25 ( 4756 hom., cov: 32)

Exomes 𝑓: 0.27 ( 55392 hom. )

Consequence

F5
NM_000130.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.12

Publications

23 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=-0.88).

BP6

Variant 1-169542789-T-C is Benign according to our data. Variant chr1-169542789-T-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 255196.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.12 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.334 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	F5	NM_000130.5	MANE Select	c.2301A>G	p.Ser767Ser	synonymous	Exon 13 of 25	NP_000121.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
F5	ENST00000367797.9	TSL:1 MANE Select	c.2301A>G	p.Ser767Ser	synonymous	Exon 13 of 25	ENSP00000356771.3
F5	ENST00000367796.3	TSL:5	c.2316A>G	p.Ser772Ser	synonymous	Exon 13 of 25	ENSP00000356770.3
F5	ENST00000904428.1		c.1611+7012A>G		intron	N/A	ENSP00000574487.1

Frequencies

GnomAD3 genomes

AF:

0.245

AC:

37285

AN:

152018

Hom.:

4745

Cov.:

show subpopulations

Gnomad AFR

AF:

0.183

Gnomad AMI

AF:

0.191

Gnomad AMR

AF:

0.341

Gnomad ASJ

AF:

0.169

Gnomad EAS

AF:

0.234

Gnomad SAS

AF:

0.323

Gnomad FIN

AF:

0.210

Gnomad MID

AF:

0.244

Gnomad NFE

AF:

0.266

Gnomad OTH

AF:

0.263

GnomAD2 exomes

AF:

0.278

AC:

69942

AN:

251178

AF XY:

0.278

show subpopulations

Gnomad AFR exome

AF:

0.179

Gnomad AMR exome

AF:

0.415

Gnomad ASJ exome

AF:

0.177

Gnomad EAS exome

AF:

0.221

Gnomad FIN exome

AF:

0.213

Gnomad NFE exome

AF:

0.268

Gnomad OTH exome

AF:

0.286

GnomAD4 exome

AF:

0.272

AC:

397369

AN:

1461716

Hom.:

55392

Cov.:

AF XY:

0.273

AC XY:

198335

AN XY:

727168

show subpopulations

African (AFR)

AF:

0.180

AC:

6039

AN:

33470

American (AMR)

AF:

0.409

AC:

18274

AN:

44710

Ashkenazi Jewish (ASJ)

AF:

0.176

AC:

4597

AN:

26130

East Asian (EAS)

AF:

0.226

AC:

8981

AN:

39698

South Asian (SAS)

AF:

0.325

AC:

28073

AN:

86254

European-Finnish (FIN)

AF:

0.217

AC:

11595

AN:

53416

Middle Eastern (MID)

AF:

0.276

AC:

1591

AN:

5766

European-Non Finnish (NFE)

AF:

0.272

AC:

302262

AN:

1111880

Other (OTH)

AF:

0.264

AC:

15957

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

18223

36447

54670

72894

91117

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10182

20364

30546

40728

50910

<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:

0.245

AC:

37325

AN:

152134

Hom.:

4756

Cov.:

AF XY:

0.247

AC XY:

18368

AN XY:

74372

show subpopulations

African (AFR)

AF:

0.183

AC:

7606

AN:

41520

American (AMR)

AF:

0.342

AC:

5224

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.169

AC:

585

AN:

3468

East Asian (EAS)

AF:

0.235

AC:

1214

AN:

5174

South Asian (SAS)

AF:

0.324

AC:

1559

AN:

4818

European-Finnish (FIN)

AF:

0.210

AC:

2230

AN:

10594

Middle Eastern (MID)

AF:

0.235

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.267

AC:

18114

AN:

67966

Other (OTH)

AF:

0.260

AC:

550

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1457

2914

4372

5829

7286

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

394

788

1182

1576

1970

<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:

0.253

Hom.:

2191

Bravo

AF:

0.254

Asia WGS

AF:

0.283

AC:

983

AN:

3478

EpiCase

AF:

0.269

EpiControl

AF:

0.270

ClinVar

ClinVar submissions as Germline

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (3)

not provided (2)

Thrombophilia due to activated protein C resistance (2)

Budd-Chiari syndrome (1)

Congenital factor V deficiency (1)

Factor V deficiency (1)

Thrombophilia due to thrombin defect (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.48

(source)

DANN

Benign

0.58

PhyloP100

-1.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over