Genetic Variant F5:c.1397-284G>C (chr1-169550299-C-G) – 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.1397-284G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.27 ( 5720 hom., cov: 16)

Consequence

F5
NM_000130.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.00

Publications

1 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=-0.9).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.377 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
F5	NM_000130.5 link	c.1397-284G>C		intron_variant	Intron 9 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.1397-284G>C		intron_variant	Intron 9 of 24	1	NM_000130.5	ENSP00000356771.3
F5	ENST00000367796.3 link	c.1397-284G>C		intron_variant	Intron 9 of 24	5		ENSP00000356770.3

Frequencies

GnomAD3 genomes

AF:

0.271

AC:

32796

AN:

121054

Hom.:

5723

Cov.:

show subpopulations

Gnomad AFR

AF:

0.161

Gnomad AMI

AF:

0.499

Gnomad AMR

AF:

0.218

Gnomad ASJ

AF:

0.353

Gnomad EAS

AF:

0.00196

Gnomad SAS

AF:

0.131

Gnomad FIN

AF:

0.204

Gnomad MID

AF:

0.347

Gnomad NFE

AF:

0.382

Gnomad OTH

AF:

0.283

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

GnomAD4 genome

AF:

0.271

AC:

32788

AN:

121150

Hom.:

5720

Cov.:

AF XY:

0.255

AC XY:

14825

AN XY:

58108

show subpopulations

African (AFR)

AF:

0.161

AC:

5370

AN:

33358

American (AMR)

AF:

0.217

AC:

2653

AN:

12208

Ashkenazi Jewish (ASJ)

AF:

0.353

AC:

1028

AN:

2916

East Asian (EAS)

AF:

0.00218

AC:

AN:

4582

South Asian (SAS)

AF:

0.131

AC:

458

AN:

3508

European-Finnish (FIN)

AF:

0.204

AC:

1479

AN:

7238

Middle Eastern (MID)

AF:

0.341

AC:

AN:

246

European-Non Finnish (NFE)

AF:

0.381

AC:

20874

AN:

54716

Other (OTH)

AF:

0.279

AC:

449

AN:

1610

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

865

1731

2596

3462

4327

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

310

620

930

1240

1550

<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:

0.134

Hom.:

306

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

4.2

(source)

DANN

Benign

0.29

PhyloP100

0.0

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