NM_000130.5:c.587-296G>A

Variant names:

• chr1-169559592-C-T
• rs6427202
• NM_000130.5:c.587-296G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000130.5(F5):​c.587-296G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.673 in 151,888 control chromosomes in the GnomAD database, including 35,596 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.67 (35596 hom., cov: 31)
• Consequence: F5 NM_000130.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.702
• Publications: 14 publications found

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

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 1-169559592-C-T is Benign according to our data. Variant chr1-169559592-C-T is described in ClinVar as Benign. ClinVar VariationId is 1239765.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.859 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
F5	NM_000130.5	c.587-296G>A		intron_variant	Intron 4 of 24	ENST00000367797.9	NP_000121.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
F5	ENST00000367797.9	c.587-296G>A		intron_variant	Intron 4 of 24	1	NM_000130.5	ENSP00000356771.3
F5	ENST00000367796.3	c.587-296G>A		intron_variant	Intron 4 of 24	5		ENSP00000356770.3

Frequencies

GnomAD3 genomes AF: 0.673 AC: 102090 AN: 151770 Hom.: 35542 Cov.: 31

Gnomad AFR AF: 0.840

Gnomad AMI AF: 0.359

Gnomad AMR AF: 0.703

Gnomad ASJ AF: 0.588

Gnomad EAS AF: 0.881

Gnomad SAS AF: 0.586

Gnomad FIN AF: 0.662

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.566

Gnomad OTH AF: 0.662

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

GnomAD4 genome AF: 0.673 AC: 102206 AN: 151888 Hom.: 35596 Cov.: 31 AF XY: 0.677 AC XY: 50236 AN XY: 74242

African (AFR) AF: 0.840 AC: 34814 AN: 41446

American (AMR) AF: 0.703 AC: 10726 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.588 AC: 2038 AN: 3464

East Asian (EAS) AF: 0.880 AC: 4546 AN: 5166

South Asian (SAS) AF: 0.585 AC: 2809 AN: 4800

European-Finnish (FIN) AF: 0.662 AC: 6979 AN: 10548

Middle Eastern (MID) AF: 0.548 AC: 161 AN: 294

European-Non Finnish (NFE) AF: 0.566 AC: 38404 AN: 67890

Other (OTH) AF: 0.663 AC: 1402 AN: 2116

Alfa AF: 0.604 Hom.: 51743

Bravo AF: 0.688

Asia WGS AF: 0.771 AC: 2681 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Nov 11, 2018

GeneDx

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	-0.80
CADD	Benign	7.1
DANN	Benign	0.64
PhyloP100		0.70
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6427202; hg19: chr1-169528830;