Genetic Variant F5:c.730+535A>G (chr1-169558618-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.730+535A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.355 in 152,014 control chromosomes in the GnomAD database, including 13,524 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 0.35 ( 13524 hom., cov: 32)

Consequence

F5
NM_000130.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.16

Publications

5 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=-0.93).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.684 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
F5	NM_000130.5 link	c.730+535A>G		intron_variant	Intron 5 of 24	ENST00000367797.9	NP_000121.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
F5	ENST00000367797.9 link	c.730+535A>G		intron_variant	Intron 5 of 24	1	NM_000130.5	ENSP00000356771.3
F5	ENST00000367796.3 link	c.730+535A>G		intron_variant	Intron 5 of 24	5		ENSP00000356770.3

Frequencies

GnomAD3 genomes

AF:

0.354

AC:

53814

AN:

151896

Hom.:

13485

Cov.:

show subpopulations

Gnomad AFR

AF:

0.690

Gnomad AMI

AF:

0.0877

Gnomad AMR

AF:

0.309

Gnomad ASJ

AF:

0.208

Gnomad EAS

AF:

0.652

Gnomad SAS

AF:

0.195

Gnomad FIN

AF:

0.255

Gnomad MID

AF:

0.171

Gnomad NFE

AF:

0.177

Gnomad OTH

AF:

0.325

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

GnomAD4 genome

AF:

0.355

AC:

53907

AN:

152014

Hom.:

13524

Cov.:

AF XY:

0.356

AC XY:

26464

AN XY:

74320

show subpopulations

African (AFR)

AF:

0.691

AC:

28611

AN:

41426

American (AMR)

AF:

0.309

AC:

4715

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.208

AC:

722

AN:

3472

East Asian (EAS)

AF:

0.651

AC:

3367

AN:

5170

South Asian (SAS)

AF:

0.194

AC:

937

AN:

4822

European-Finnish (FIN)

AF:

0.255

AC:

2690

AN:

10556

Middle Eastern (MID)

AF:

0.177

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.177

AC:

12033

AN:

67974

Other (OTH)

AF:

0.331

AC:

700

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1402

2804

4206

5608

7010

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

458

916

1374

1832

2290

<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:

0.237

Hom.:

20450

Bravo

AF:

0.377

Asia WGS

AF:

0.458

AC:

1592

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.74

(source)

DANN

Benign

0.59

PhyloP100

-1.2

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