rs2420370

Positions:

• chr1-169521154-G-C

Variant summary

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

The NM_000130.5(F5):​c.6049-490C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.953 in 152,096 control chromosomes in the GnomAD database, including 69,088 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 0.95 (69088 hom., cov: 30)
• Consequence: F5 NM_000130.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0770

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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
F5	NM_000130.5	c.6049-490C>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.6049-490C>G		intron_variant		1	NM_000130.5	ENSP00000356771	P2
F5	ENST00000367796.3	c.6064-490C>G		intron_variant		5		ENSP00000356770	A2

Frequencies

GnomAD3 genomes AF: 0.953 AC: 144804 AN: 151978 Hom.: 69028 Cov.: 30

Gnomad AFR AF: 0.983

Gnomad AMI AF: 0.892

Gnomad AMR AF: 0.960

Gnomad ASJ AF: 0.912

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.934

Gnomad FIN AF: 0.951

Gnomad MID AF: 0.873

Gnomad NFE AF: 0.934

Gnomad OTH AF: 0.947

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

GnomAD4 genome AF: 0.953 AC: 144925 AN: 152096 Hom.: 69088 Cov.: 30 AF XY: 0.954 AC XY: 70920 AN XY: 74336

Gnomad4 AFR AF: 0.983

Gnomad4 AMR AF: 0.960

Gnomad4 ASJ AF: 0.912

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.935

Gnomad4 FIN AF: 0.951

Gnomad4 NFE AF: 0.934

Gnomad4 OTH AF: 0.947

Alfa AF: 0.946 Hom.: 8458

Bravo AF: 0.954

Asia WGS AF: 0.976 AC: 3396 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	3.0
DANN	Benign	0.38

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: rs2420370; hg19: chr1-169490392;