1-169582444-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.237A>G(p.Gln79Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.271 in 1,507,572 control chromosomes in the GnomAD database, including 58,939 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.23 ( 4921 hom., cov: 33)

Exomes 𝑓: 0.28 ( 54018 hom. )

Consequence

F5
NM_000130.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.610

Publications

38 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=-0.61).

BP6

Variant 1-169582444-T-C is Benign according to our data. Variant chr1-169582444-T-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 255197.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.61 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.344 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
F5	NM_000130.5 link	c.237A>G	p.Gln79Gln	synonymous_variant	Exon 2 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.237A>G	p.Gln79Gln	synonymous_variant	Exon 2 of 25	1	NM_000130.5	ENSP00000356771.3
F5	ENST00000367796.3 link	c.237A>G	p.Gln79Gln	synonymous_variant	Exon 2 of 25	5		ENSP00000356770.3

Frequencies

GnomAD3 genomes

AF:

0.231

AC:

35185

AN:

152090

Hom.:

4909

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0677

Gnomad AMI

AF:

0.153

Gnomad AMR

AF:

0.322

Gnomad ASJ

AF:

0.263

Gnomad EAS

AF:

0.219

Gnomad SAS

AF:

0.357

Gnomad FIN

AF:

0.353

Gnomad MID

AF:

0.239

Gnomad NFE

AF:

0.283

Gnomad OTH

AF:

0.248

GnomAD2 exomes

AF:

0.291

AC:

70058

AN:

240928

AF XY:

0.291

show subpopulations

Gnomad AFR exome

AF:

0.0623

Gnomad AMR exome

AF:

0.431

Gnomad ASJ exome

AF:

0.259

Gnomad EAS exome

AF:

0.191

Gnomad FIN exome

AF:

0.343

Gnomad NFE exome

AF:

0.280

Gnomad OTH exome

AF:

0.270

GnomAD4 exome

AF:

0.275

AC:

373211

AN:

1355362

Hom.:

54018

Cov.:

AF XY:

0.278

AC XY:

188256

AN XY:

678108

show subpopulations

African (AFR)

AF:

0.0545

AC:

1752

AN:

32174

American (AMR)

AF:

0.415

AC:

17554

AN:

42274

Ashkenazi Jewish (ASJ)

AF:

0.258

AC:

6452

AN:

25034

East Asian (EAS)

AF:

0.255

AC:

9934

AN:

38920

South Asian (SAS)

AF:

0.335

AC:

26823

AN:

80186

European-Finnish (FIN)

AF:

0.339

AC:

17760

AN:

52338

Middle Eastern (MID)

AF:

0.207

AC:

1143

AN:

5532

European-Non Finnish (NFE)

AF:

0.271

AC:

277408

AN:

1022328

Other (OTH)

AF:

0.254

AC:

14385

AN:

56576

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.436

Heterozygous variant carriers

10706

21412

32119

42825

53531

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8986

17972

26958

35944

44930

<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:

0.231

AC:

35201

AN:

152210

Hom.:

4921

Cov.:

AF XY:

0.237

AC XY:

17667

AN XY:

74400

show subpopulations

African (AFR)

AF:

0.0675

AC:

2806

AN:

41570

American (AMR)

AF:

0.323

AC:

4942

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.263

AC:

913

AN:

3468

East Asian (EAS)

AF:

0.219

AC:

1138

AN:

5194

South Asian (SAS)

AF:

0.358

AC:

1725

AN:

4824

European-Finnish (FIN)

AF:

0.353

AC:

3726

AN:

10560

Middle Eastern (MID)

AF:

0.238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.283

AC:

19227

AN:

67984

Other (OTH)

AF:

0.244

AC:

515

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1327

2654

3981

5308

6635

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

388

776

1164

1552

1940

<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:

0.261

Hom.:

16624

Bravo

AF:

0.223

Asia WGS

AF:

0.273

AC:

946

AN:

3468

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

not provided

Benign:2

May 04, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

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

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

-0.61

CADD

Benign

5.5

(source)

DANN

Benign

0.53

PhyloP100

0.61

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