rs2227245

Positions:

• chr1-169570842-C-T

Variant summary

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

The NM_000130.5(F5):​c.373+1379G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.279 in 151,884 control chromosomes in the GnomAD database, including 6,240 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 0.28 (6240 hom., cov: 32)
• Consequence: F5 NM_000130.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.636

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=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.355 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
F5	NM_000130.5	c.373+1379G>A		intron_variant		ENST00000367797.9	NP_000121.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
F5	ENST00000367797.9	c.373+1379G>A		intron_variant		1	NM_000130.5	ENSP00000356771	P2
F5	ENST00000367796.3	c.373+1379G>A		intron_variant		5		ENSP00000356770	A2

Frequencies

GnomAD3 genomes AF: 0.279 AC: 42386 AN: 151766 Hom.: 6228 Cov.: 32

Gnomad AFR AF: 0.187

Gnomad AMI AF: 0.152

Gnomad AMR AF: 0.346

Gnomad ASJ AF: 0.269

Gnomad EAS AF: 0.303

Gnomad SAS AF: 0.369

Gnomad FIN AF: 0.371

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.300

Gnomad OTH AF: 0.287

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

GnomAD4 genome AF: 0.279 AC: 42425 AN: 151884 Hom.: 6240 Cov.: 32 AF XY: 0.285 AC XY: 21167 AN XY: 74210

Gnomad4 AFR AF: 0.187

Gnomad4 AMR AF: 0.347

Gnomad4 ASJ AF: 0.269

Gnomad4 EAS AF: 0.304

Gnomad4 SAS AF: 0.369

Gnomad4 FIN AF: 0.371

Gnomad4 NFE AF: 0.300

Gnomad4 OTH AF: 0.282

Alfa AF: 0.297 Hom.: 7014

Bravo AF: 0.275

Asia WGS AF: 0.313 AC: 1090 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	6.8
DANN	Benign	0.65

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: rs2227245; hg19: chr1-169540080;