rs9332579

Variant names:

• chr1-169556074-C-T
• rs9332579
• NM_000130.5:c.952+572G>A

Variant summary

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

The NM_000130.5(F5):​c.952+572G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.191 in 151,992 control chromosomes in the GnomAD database, including 4,117 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 0.19 (4117 hom., cov: 32)
• Consequence: F5 NM_000130.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.40
• Publications: 5 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: Genomics England PanelApp, ClinGen, Labcorp Genetics (formerly Invitae)
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.396 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.952+572G>A		intron	N/A	NP_000121.2	P12259

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	F5	ENST00000367797.9	TSL:1 MANE Select	c.952+572G>A		intron	N/A	ENSP00000356771.3	P12259
	F5	ENST00000367796.3	TSL:5	c.952+572G>A		intron	N/A	ENSP00000356770.3	A0A0A0MRJ7
	F5	ENST00000904428.1		c.952+572G>A		intron	N/A	ENSP00000574487.1

Frequencies

GnomAD3 genomes AF: 0.191 AC: 29074 AN: 151874 Hom.: 4112 Cov.: 32

Gnomad AFR AF: 0.402

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.125

Gnomad ASJ AF: 0.0897

Gnomad EAS AF: 0.000963

Gnomad SAS AF: 0.0323

Gnomad FIN AF: 0.102

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.127

Gnomad OTH AF: 0.174

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

GnomAD4 genome AF: 0.191 AC: 29095 AN: 151992 Hom.: 4117 Cov.: 32 AF XY: 0.183 AC XY: 13629 AN XY: 74316

African (AFR) AF: 0.401 AC: 16604 AN: 41388

American (AMR) AF: 0.125 AC: 1907 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0897 AC: 311 AN: 3468

East Asian (EAS) AF: 0.000965 AC: 5 AN: 5180

South Asian (SAS) AF: 0.0321 AC: 155 AN: 4828

European-Finnish (FIN) AF: 0.102 AC: 1075 AN: 10590

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.127 AC: 8640 AN: 67944

Other (OTH) AF: 0.171 AC: 361 AN: 2108

Alfa AF: 0.162 Hom.: 4080

Bravo AF: 0.205

Asia WGS AF: 0.0400 AC: 142 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.096
DANN	Benign	0.75
PhyloP100		-1.4
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: rs9332579; hg19: chr1-169525312;