rs2420371

Variant names:

• chr1-169522317-G-A
• rs2420371
• NM_000130.5:c.6048+880C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-169522317-G-A
• chr1-169522317-G-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.6048+880C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.955 in 152,250 control chromosomes in the GnomAD database, including 69,405 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 0.95 (69405 hom., cov: 31)
• Consequence: F5 NM_000130.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0630
• Publications: 21 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.981 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.6048+880C>T		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.6048+880C>T		intron	N/A	ENSP00000356771.3
	F5	ENST00000367796.3	TSL:5	c.6063+880C>T		intron	N/A	ENSP00000356770.3

Frequencies

GnomAD3 genomes AF: 0.954 AC: 145199 AN: 152132 Hom.: 69341 Cov.: 31

Gnomad AFR AF: 0.989

Gnomad AMI AF: 0.893

Gnomad AMR AF: 0.961

Gnomad ASJ AF: 0.912

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.935

Gnomad FIN AF: 0.950

Gnomad MID AF: 0.873

Gnomad NFE AF: 0.934

Gnomad OTH AF: 0.948

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

GnomAD4 genome AF: 0.955 AC: 145324 AN: 152250 Hom.: 69405 Cov.: 31 AF XY: 0.956 AC XY: 71143 AN XY: 74438

African (AFR) AF: 0.989 AC: 41088 AN: 41556

American (AMR) AF: 0.962 AC: 14699 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.912 AC: 3165 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5188 AN: 5190

South Asian (SAS) AF: 0.936 AC: 4505 AN: 4814

European-Finnish (FIN) AF: 0.950 AC: 10073 AN: 10600

Middle Eastern (MID) AF: 0.874 AC: 257 AN: 294

European-Non Finnish (NFE) AF: 0.934 AC: 63532 AN: 68016

Other (OTH) AF: 0.949 AC: 2004 AN: 2112

Alfa AF: 0.939 Hom.: 171120

Bravo AF: 0.956

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.63
DANN	Benign	0.41
PhyloP100		0.063
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: rs2420371; hg19: chr1-169491555;