1-169561599-G-T

Variant summary

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

The NM_000130.5(F5):c.374-833C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.273 in 151,998 control chromosomes in the GnomAD database, including 6,008 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 (6008 hom., cov: 32)
• Consequence: F5 NM_000130.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.26

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=-1.01).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.346 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
F5	NM_000130.5	c.374-833C>A		intron_variant		ENST00000367797.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
F5	ENST00000367797.9	c.374-833C>A		intron_variant		1	NM_000130.5	P2
F5	ENST00000367796.3	c.374-833C>A		intron_variant		5		A2

Frequencies

GnomAD3 genomes AF: 0.273 AC: 41446 AN: 151880 Hom.: 5996 Cov.: 32

Gnomad AFR AF: 0.178

Gnomad AMI AF: 0.153

Gnomad AMR AF: 0.344

Gnomad ASJ AF: 0.268

Gnomad EAS AF: 0.219

Gnomad SAS AF: 0.360

Gnomad FIN AF: 0.367

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.300

Gnomad OTH AF: 0.279

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

GnomAD4 genome AF: 0.273 AC: 41484 AN: 151998 Hom.: 6008 Cov.: 32 AF XY: 0.278 AC XY: 20667 AN XY: 74294

Gnomad4 AFR AF: 0.178

Gnomad4 AMR AF: 0.345

Gnomad4 ASJ AF: 0.268

Gnomad4 EAS AF: 0.220

Gnomad4 SAS AF: 0.360

Gnomad4 FIN AF: 0.367

Gnomad4 NFE AF: 0.300

Gnomad4 OTH AF: 0.275

Alfa AF: 0.290 Hom.: 13171

Bravo AF: 0.268

Asia WGS AF: 0.283 AC: 984 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.0010
Dann	Benign	0.46

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: rs1894702; hg19: chr1-169530837;