rs2420371

chr1-169522317-G-Achr1-169522317-G-C

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
F5	NM_000130.5	c.6048+880C>T		intron_variant		ENST00000367797.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
F5	ENST00000367797.9	c.6048+880C>T		intron_variant		1	NM_000130.5	P2
F5	ENST00000367796.3	c.6063+880C>T		intron_variant		5		A2

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

Gnomad4 AFR AF: 0.989

Gnomad4 AMR AF: 0.962

Gnomad4 ASJ AF: 0.912

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.936

Gnomad4 FIN AF: 0.950

Gnomad4 NFE AF: 0.934

Gnomad4 OTH AF: 0.949

Alfa AF: 0.936 Hom.: 67654

Bravo AF: 0.956

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	0.63
Dann	Benign	0.41

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

Publications

LitVar

Other links and lift over

dbSNP: rs2420371; hg19: chr1-169491555;