1-169567201-C-T

Variant names:

• chr1-169567201-C-T
• rs7542281
• NM_000130.5:c.373+5020G>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.373+5020G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.241 in 151,518 control chromosomes in the GnomAD database, including 5,298 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 0.24 (5298 hom., cov: 30)
• Consequence: F5 NM_000130.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.268
• Publications: 7 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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.346 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.373+5020G>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.373+5020G>A		intron	N/A	ENSP00000356771.3	P12259
	F5	ENST00000367796.3	TSL:5	c.373+5020G>A		intron	N/A	ENSP00000356770.3	A0A0A0MRJ7
	F5	ENST00000904428.1		c.373+5020G>A		intron	N/A	ENSP00000574487.1

Frequencies

GnomAD3 genomes AF: 0.241 AC: 36504 AN: 151398 Hom.: 5286 Cov.: 30

Gnomad AFR AF: 0.0710

Gnomad AMI AF: 0.152

Gnomad AMR AF: 0.327

Gnomad ASJ AF: 0.264

Gnomad EAS AF: 0.217

Gnomad SAS AF: 0.359

Gnomad FIN AF: 0.368

Gnomad MID AF: 0.239

Gnomad NFE AF: 0.299

Gnomad OTH AF: 0.255

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

GnomAD4 genome AF: 0.241 AC: 36520 AN: 151518 Hom.: 5298 Cov.: 30 AF XY: 0.246 AC XY: 18227 AN XY: 73974

African (AFR) AF: 0.0708 AC: 2933 AN: 41398

American (AMR) AF: 0.329 AC: 4975 AN: 15144

Ashkenazi Jewish (ASJ) AF: 0.264 AC: 918 AN: 3472

East Asian (EAS) AF: 0.217 AC: 1105 AN: 5082

South Asian (SAS) AF: 0.360 AC: 1727 AN: 4800

European-Finnish (FIN) AF: 0.368 AC: 3848 AN: 10462

Middle Eastern (MID) AF: 0.238 AC: 70 AN: 294

European-Non Finnish (NFE) AF: 0.299 AC: 20279 AN: 67854

Other (OTH) AF: 0.250 AC: 526 AN: 2100

Alfa AF: 0.273 Hom.: 8932

Bravo AF: 0.232

Asia WGS AF: 0.275 AC: 955 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	11
DANN	Benign	0.73
PhyloP100		0.27
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: rs7542281; hg19: chr1-169536439;