rs9332627

Variant names:

• chr1-169528582-G-A
• rs9332627
• NM_000130.5:c.5420-488C>T

Variant summary

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

The NM_000130.5(F5):​c.5420-488C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.246 in 151,974 control chromosomes in the GnomAD database, including 4,804 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 0.25 (4804 hom., cov: 32)
• Consequence: F5 NM_000130.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.201

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=-0.86).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.336 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
F5	NM_000130.5	c.5420-488C>T		intron_variant	Intron 16 of 24	ENST00000367797.9	NP_000121.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
F5	ENST00000367797.9	c.5420-488C>T		intron_variant	Intron 16 of 24	1	NM_000130.5	ENSP00000356771.3
F5	ENST00000367796.3	c.5435-488C>T		intron_variant	Intron 16 of 24	5		ENSP00000356770.3

Frequencies

GnomAD3 genomes AF: 0.246 AC: 37334 AN: 151856 Hom.: 4795 Cov.: 32

Gnomad AFR AF: 0.187

Gnomad AMI AF: 0.191

Gnomad AMR AF: 0.343

Gnomad ASJ AF: 0.166

Gnomad EAS AF: 0.236

Gnomad SAS AF: 0.326

Gnomad FIN AF: 0.205

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.265

Gnomad OTH AF: 0.263

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

GnomAD4 genome AF: 0.246 AC: 37361 AN: 151974 Hom.: 4804 Cov.: 32 AF XY: 0.248 AC XY: 18393 AN XY: 74288

Gnomad4 AFR AF: 0.187

Gnomad4 AMR AF: 0.344

Gnomad4 ASJ AF: 0.166

Gnomad4 EAS AF: 0.236

Gnomad4 SAS AF: 0.327

Gnomad4 FIN AF: 0.205

Gnomad4 NFE AF: 0.265

Gnomad4 OTH AF: 0.261

Alfa AF: 0.270 Hom.: 3105

Bravo AF: 0.256

Asia WGS AF: 0.279 AC: 971 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.5
DANN	Benign	0.40

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: rs9332627; hg19: chr1-169497820;