1-169535920-T-C

Position:

• chr1-169535920-T-C

Variant summary

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

The NM_000130.5(F5):​c.4971+586A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.401 in 151,932 control chromosomes in the GnomAD database, including 13,218 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 0.40 (13218 hom., cov: 32)
• Consequence: F5 NM_000130.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.77

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.874 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
F5	NM_000130.5	c.4971+586A>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.4971+586A>G		intron_variant		1	NM_000130.5	ENSP00000356771.3
F5	ENST00000367796.3	c.4986+586A>G		intron_variant		5		ENSP00000356770.3

Frequencies

GnomAD3 genomes AF: 0.401 AC: 60808 AN: 151814 Hom.: 13192 Cov.: 32

Gnomad AFR AF: 0.384

Gnomad AMI AF: 0.194

Gnomad AMR AF: 0.540

Gnomad ASJ AF: 0.285

Gnomad EAS AF: 0.895

Gnomad SAS AF: 0.563

Gnomad FIN AF: 0.377

Gnomad MID AF: 0.357

Gnomad NFE AF: 0.342

Gnomad OTH AF: 0.415

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

GnomAD4 genome AF: 0.401 AC: 60876 AN: 151932 Hom.: 13218 Cov.: 32 AF XY: 0.412 AC XY: 30578 AN XY: 74236

Gnomad4 AFR AF: 0.384

Gnomad4 AMR AF: 0.541

Gnomad4 ASJ AF: 0.285

Gnomad4 EAS AF: 0.895

Gnomad4 SAS AF: 0.563

Gnomad4 FIN AF: 0.377

Gnomad4 NFE AF: 0.342

Gnomad4 OTH AF: 0.420

Alfa AF: 0.355 Hom.: 13182

Bravo AF: 0.414

Asia WGS AF: 0.714 AC: 2482 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.20
DANN	Benign	0.29

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: rs4656687; hg19: chr1-169505158;