1-169584820-C-G

Variant names:

• chr1-169584820-C-G
• rs3753305
• NM_000130.5:c.158+1409G>C

Variant summary

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

The NM_000130.5(F5):​c.158+1409G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.666 in 152,074 control chromosomes in the GnomAD database, including 35,007 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 0.67 (35007 hom., cov: 32)
• Consequence: F5 NM_000130.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.917
• Publications: 18 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.86 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	F5	NM_000130.5	MANE Select	c.158+1409G>C		intron	N/A	NP_000121.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	F5	ENST00000367797.9	TSL:1 MANE Select	c.158+1409G>C		intron	N/A	ENSP00000356771.3
	F5	ENST00000367796.3	TSL:5	c.158+1409G>C		intron	N/A	ENSP00000356770.3
	F5	ENST00000904428.1		c.158+1409G>C		intron	N/A	ENSP00000574487.1

Frequencies

GnomAD3 genomes AF: 0.666 AC: 101196 AN: 151956 Hom.: 34953 Cov.: 32

Gnomad AFR AF: 0.837

Gnomad AMI AF: 0.359

Gnomad AMR AF: 0.700

Gnomad ASJ AF: 0.587

Gnomad EAS AF: 0.882

Gnomad SAS AF: 0.589

Gnomad FIN AF: 0.647

Gnomad MID AF: 0.547

Gnomad NFE AF: 0.555

Gnomad OTH AF: 0.657

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

GnomAD4 genome AF: 0.666 AC: 101312 AN: 152074 Hom.: 35007 Cov.: 32 AF XY: 0.671 AC XY: 49853 AN XY: 74328

African (AFR) AF: 0.837 AC: 34757 AN: 41506

American (AMR) AF: 0.701 AC: 10701 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.587 AC: 2035 AN: 3468

East Asian (EAS) AF: 0.882 AC: 4571 AN: 5184

South Asian (SAS) AF: 0.589 AC: 2839 AN: 4818

European-Finnish (FIN) AF: 0.647 AC: 6835 AN: 10566

Middle Eastern (MID) AF: 0.554 AC: 163 AN: 294

European-Non Finnish (NFE) AF: 0.555 AC: 37694 AN: 67938

Other (OTH) AF: 0.658 AC: 1390 AN: 2114

Alfa AF: 0.625 Hom.: 3774

Bravo AF: 0.682

Asia WGS AF: 0.771 AC: 2681 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	6.4
DANN	Benign	0.38
PhyloP100		0.92
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: rs3753305; hg19: chr1-169554058;