Genetic Variant F5:c.373+5292A>G (chr1-169566929-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000130.5(F5):c.373+5292A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.304 in 151,830 control chromosomes in the GnomAD database, including 8,952 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.30 ( 8952 hom., cov: 32)

Consequence

F5
NM_000130.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.195

Publications

8 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.635 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
F5	NM_000130.5 link	c.373+5292A>G		intron_variant	Intron 3 of 24	ENST00000367797.9	NP_000121.2	P12259

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
F5	ENST00000367797.9 link	c.373+5292A>G		intron_variant	Intron 3 of 24	1	NM_000130.5	ENSP00000356771.3		P12259
F5	ENST00000367796.3 link	c.373+5292A>G		intron_variant	Intron 3 of 24	5		ENSP00000356770.3		A0A0A0MRJ7

Frequencies

GnomAD3 genomes

AF:

0.304

AC:

46073

AN:

151712

Hom.:

8942

Cov.:

show subpopulations

Gnomad AFR

AF:

0.517

Gnomad AMI

AF:

0.0877

Gnomad AMR

AF:

0.285

Gnomad ASJ

AF:

0.205

Gnomad EAS

AF:

0.654

Gnomad SAS

AF:

0.193

Gnomad FIN

AF:

0.254

Gnomad MID

AF:

0.161

Gnomad NFE

AF:

0.177

Gnomad OTH

AF:

0.284

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.304

AC:

46114

AN:

151830

Hom.:

8952

Cov.:

AF XY:

0.306

AC XY:

22703

AN XY:

74200

show subpopulations

African (AFR)

AF:

0.517

AC:

21389

AN:

41380

American (AMR)

AF:

0.285

AC:

4335

AN:

15230

Ashkenazi Jewish (ASJ)

AF:

0.205

AC:

711

AN:

3468

East Asian (EAS)

AF:

0.653

AC:

3344

AN:

5120

South Asian (SAS)

AF:

0.192

AC:

927

AN:

4820

European-Finnish (FIN)

AF:

0.254

AC:

2683

AN:

10554

Middle Eastern (MID)

AF:

0.167

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.176

AC:

11991

AN:

67944

Other (OTH)

AF:

0.287

AC:

605

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1424

2847

4271

5694

7118

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

428

856

1284

1712

2140

<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:

0.263

Hom.:

2299

Bravo

AF:

0.319

Asia WGS

AF:

0.448

AC:

1556

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

2.0

(source)

DANN

Benign

0.85

PhyloP100

-0.20

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over