rs2420369

Variant names:

• chr1-169516621-T-A
• rs2420369
• NM_000130.5:c.6346-995A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000130.5(F5):​c.6346-995A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.494 in 152,042 control chromosomes in the GnomAD database, including 19,007 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 0.49 (19007 hom., cov: 33)
• Consequence: F5 NM_000130.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.68
• Publications: 6 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.655 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000130.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	F5	NM_000130.5	MANE Select	c.6346-995A>T		intron	N/A	NP_000121.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	F5	ENST00000367797.9	TSL:1 MANE Select	c.6346-995A>T		intron	N/A	ENSP00000356771.3
	F5	ENST00000367796.3	TSL:5	c.6361-995A>T		intron	N/A	ENSP00000356770.3
	F5	ENST00000904428.1		c.2986-995A>T		intron	N/A	ENSP00000574487.1

Frequencies

GnomAD3 genomes AF: 0.494 AC: 75018 AN: 151922 Hom.: 19005 Cov.: 33

Gnomad AFR AF: 0.409

Gnomad AMI AF: 0.663

Gnomad AMR AF: 0.401

Gnomad ASJ AF: 0.483

Gnomad EAS AF: 0.674

Gnomad SAS AF: 0.437

Gnomad FIN AF: 0.614

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.537

Gnomad OTH AF: 0.483

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

GnomAD4 genome AF: 0.494 AC: 75050 AN: 152042 Hom.: 19007 Cov.: 33 AF XY: 0.494 AC XY: 36705 AN XY: 74334

African (AFR) AF: 0.409 AC: 16967 AN: 41472

American (AMR) AF: 0.400 AC: 6110 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.483 AC: 1674 AN: 3468

East Asian (EAS) AF: 0.673 AC: 3483 AN: 5172

South Asian (SAS) AF: 0.438 AC: 2112 AN: 4822

European-Finnish (FIN) AF: 0.614 AC: 6491 AN: 10574

Middle Eastern (MID) AF: 0.411 AC: 120 AN: 292

European-Non Finnish (NFE) AF: 0.537 AC: 36466 AN: 67956

Other (OTH) AF: 0.483 AC: 1022 AN: 2114

Alfa AF: 0.505 Hom.: 2493

Bravo AF: 0.478

Asia WGS AF: 0.519 AC: 1803 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	10
DANN	Benign	0.77
PhyloP100		2.7
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: rs2420369; hg19: chr1-169485859;