rs1800594

Variant names:

Your query was ambiguous. Multiple possible variants found:

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.3804T>C(p.Ser1268Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.334 in 1,581,322 control chromosomes in the GnomAD database, including 90,328 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.34 ( 7075 hom., cov: 26)

Exomes 𝑓: 0.33 ( 83253 hom. )

Consequence

F5
NM_000130.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.35

Publications

22 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=-0.96).

BP6

Variant 1-169541286-A-G is Benign according to our data. Variant chr1-169541286-A-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 255204.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.35 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.465 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.3804T>C	p.Ser1268Ser	synonymous	Exon 13 of 25	NP_000121.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	F5	ENST00000367797.9	TSL:1 MANE Select	c.3804T>C	p.Ser1268Ser	synonymous	Exon 13 of 25	ENSP00000356771.3
	F5	ENST00000367796.3	TSL:5	c.3819T>C	p.Ser1273Ser	synonymous	Exon 13 of 25	ENSP00000356770.3

Frequencies

GnomAD3 genomes

AF:

0.339

AC:

44420

AN:

130954

Hom.:

7063

Cov.:

show subpopulations

Gnomad AFR

AF:

0.237

Gnomad AMI

AF:

0.242

Gnomad AMR

AF:

0.474

Gnomad ASJ

AF:

0.271

Gnomad EAS

AF:

0.315

Gnomad SAS

AF:

0.433

Gnomad FIN

AF:

0.347

Gnomad MID

AF:

0.409

Gnomad NFE

AF:

0.361

Gnomad OTH

AF:

0.369

GnomAD2 exomes

AF:

0.343

AC:

85016

AN:

247572

AF XY:

0.344

show subpopulations

Gnomad AFR exome

AF:

0.188

Gnomad AMR exome

AF:

0.514

Gnomad ASJ exome

AF:

0.244

Gnomad EAS exome

AF:

0.254

Gnomad FIN exome

AF:

0.298

Gnomad NFE exome

AF:

0.330

Gnomad OTH exome

AF:

0.360

GnomAD4 exome

AF:

0.334

AC:

483672

AN:

1450290

Hom.:

83253

Cov.:

AF XY:

0.335

AC XY:

241822

AN XY:

721128

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.192

AC:

6362

AN:

33098

American (AMR)

AF:

0.507

AC:

22063

AN:

43514

Ashkenazi Jewish (ASJ)

AF:

0.246

AC:

6340

AN:

25816

East Asian (EAS)

AF:

0.287

AC:

11330

AN:

39500

South Asian (SAS)

AF:

0.399

AC:

33853

AN:

84904

European-Finnish (FIN)

AF:

0.300

AC:

15964

AN:

53178

Middle Eastern (MID)

AF:

0.366

AC:

2093

AN:

5726

European-Non Finnish (NFE)

AF:

0.331

AC:

366130

AN:

1104698

Other (OTH)

AF:

0.326

AC:

19537

AN:

59856

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.398

Heterozygous variant carriers

15755

31510

47266

63021

78776

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11836

23672

35508

47344

59180

<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:

0.339

AC:

44460

AN:

131032

Hom.:

7075

Cov.:

AF XY:

0.344

AC XY:

21950

AN XY:

63882

show subpopulations

African (AFR)

AF:

0.237

AC:

7828

AN:

32980

American (AMR)

AF:

0.474

AC:

6611

AN:

13940

Ashkenazi Jewish (ASJ)

AF:

0.271

AC:

842

AN:

3112

East Asian (EAS)

AF:

0.316

AC:

1298

AN:

4112

South Asian (SAS)

AF:

0.434

AC:

1816

AN:

4184

European-Finnish (FIN)

AF:

0.347

AC:

2956

AN:

8528

Middle Eastern (MID)

AF:

0.402

AC:

AN:

214

European-Non Finnish (NFE)

AF:

0.361

AC:

22174

AN:

61408

Other (OTH)

AF:

0.368

AC:

675

AN:

1834

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1431

2862

4292

5723

7154

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

450

900

1350

1800

2250

<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:

0.318

Hom.:

3268

Asia WGS

AF:

0.331

AC:

1129

AN:

3416

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

-0.96

CADD

Benign

0.059

(source)

DANN

Benign

0.29

PhyloP100

-1.4

Mutation Taster

=98/2

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

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over