rs10489184

Positions:

• chr1-169579802-T-C
• chr1-169579802-T-G

Variant summary

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

The NM_000130.5(F5):​c.250+2629A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0871 in 152,286 control chromosomes in the GnomAD database, including 668 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 0.087 (668 hom., cov: 32)
• Consequence: F5 NM_000130.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.401

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 (AFR) allele frequency at 95% confidence interval = 0.115 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
F5	NM_000130.5	c.250+2629A>G		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+2629A>G		intron_variant		1	NM_000130.5	ENSP00000356771	P2
F5	ENST00000367796.3	c.250+2629A>G		intron_variant		5		ENSP00000356770	A2

Frequencies

GnomAD3 genomes AF: 0.0870 AC: 13243 AN: 152168 Hom.: 666 Cov.: 32

Gnomad AFR AF: 0.118

Gnomad AMI AF: 0.121

Gnomad AMR AF: 0.0739

Gnomad ASJ AF: 0.107

Gnomad EAS AF: 0.00769

Gnomad SAS AF: 0.0333

Gnomad FIN AF: 0.0377

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.0870

Gnomad OTH AF: 0.0919

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

GnomAD4 genome AF: 0.0871 AC: 13259 AN: 152286 Hom.: 668 Cov.: 32 AF XY: 0.0839 AC XY: 6251 AN XY: 74472

Gnomad4 AFR AF: 0.118

Gnomad4 AMR AF: 0.0738

Gnomad4 ASJ AF: 0.107

Gnomad4 EAS AF: 0.00771

Gnomad4 SAS AF: 0.0333

Gnomad4 FIN AF: 0.0377

Gnomad4 NFE AF: 0.0870

Gnomad4 OTH AF: 0.0900

Alfa AF: 0.0372 Hom.: 27

Bravo AF: 0.0919

Asia WGS AF: 0.0420 AC: 149 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	4.7
DANN	Benign	0.82

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: rs10489184; hg19: chr1-169549040;