rs9332653

chr1-169521534-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.6049-870C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.267 in 151,032 control chromosomes in the GnomAD database, including 6,429 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 0.27 (6429 hom., cov: 30)
• Consequence: F5 NM_000130.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.247

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.714 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
F5	NM_000130.5	c.6049-870C>T		intron_variant		ENST00000367797.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
F5	ENST00000367797.9	c.6049-870C>T		intron_variant		1	NM_000130.5	P2
F5	ENST00000367796.3	c.6064-870C>T		intron_variant		5		A2

Frequencies

GnomAD3 genomes AF: 0.267 AC: 40289 AN: 150916 Hom.: 6427 Cov.: 30

Gnomad AFR AF: 0.330

Gnomad AMI AF: 0.142

Gnomad AMR AF: 0.245

Gnomad ASJ AF: 0.289

Gnomad EAS AF: 0.734

Gnomad SAS AF: 0.359

Gnomad FIN AF: 0.297

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.188

Gnomad OTH AF: 0.256

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

GnomAD4 genome AF: 0.267 AC: 40326 AN: 151032 Hom.: 6429 Cov.: 30 AF XY: 0.275 AC XY: 20253 AN XY: 73716

Gnomad4 AFR AF: 0.330

Gnomad4 AMR AF: 0.245

Gnomad4 ASJ AF: 0.289

Gnomad4 EAS AF: 0.734

Gnomad4 SAS AF: 0.359

Gnomad4 FIN AF: 0.297

Gnomad4 NFE AF: 0.188

Gnomad4 OTH AF: 0.262

Alfa AF: 0.208 Hom.: 4448

Bravo AF: 0.267

Asia WGS AF: 0.532 AC: 1852 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	1.2
Dann	Benign	0.58

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: rs9332653; hg19: chr1-169490772;