rs12755775

Positions:

• chr1-169578479-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000130.5(F5):​c.250+3952C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0748 in 152,132 control chromosomes in the GnomAD database, including 585 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 0.075 (585 hom., cov: 31)
• Consequence: F5 NM_000130.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.65

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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.109 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
F5	NM_000130.5	c.250+3952C>T		intron_variant		ENST00000367797.9	NP_000121.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
F5	ENST00000367797.9	c.250+3952C>T		intron_variant		1	NM_000130.5	ENSP00000356771	P2
F5	ENST00000367796.3	c.250+3952C>T		intron_variant		5		ENSP00000356770	A2

Frequencies

GnomAD3 genomes AF: 0.0749 AC: 11384 AN: 152014 Hom.: 585 Cov.: 31

Gnomad AFR AF: 0.0313

Gnomad AMI AF: 0.0877

Gnomad AMR AF: 0.0827

Gnomad ASJ AF: 0.0386

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.0228

Gnomad FIN AF: 0.0705

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.111

Gnomad OTH AF: 0.0861

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

GnomAD4 genome AF: 0.0748 AC: 11386 AN: 152132 Hom.: 585 Cov.: 31 AF XY: 0.0719 AC XY: 5348 AN XY: 74352

Gnomad4 AFR AF: 0.0313

Gnomad4 AMR AF: 0.0825

Gnomad4 ASJ AF: 0.0386

Gnomad4 EAS AF: 0.000387

Gnomad4 SAS AF: 0.0230

Gnomad4 FIN AF: 0.0705

Gnomad4 NFE AF: 0.111

Gnomad4 OTH AF: 0.0852

Alfa AF: 0.0933 Hom.: 367

Bravo AF: 0.0734

Asia WGS AF: 0.0140 AC: 48 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.084
DANN	Benign	0.52

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: rs12755775; hg19: chr1-169547717; COSMIC: COSV63125850;