1-169528688-T-G

Position:

• chr1-169528688-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.5420-594A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0999 in 152,162 control chromosomes in the GnomAD database, including 2,002 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 0.10 (2002 hom., cov: 32)
• Consequence: F5 NM_000130.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.886

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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.616 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
F5	NM_000130.5	c.5420-594A>C		intron_variant		ENST00000367797.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
F5	ENST00000367797.9	c.5420-594A>C		intron_variant		1	NM_000130.5	P2
F5	ENST00000367796.3	c.5435-594A>C		intron_variant		5		A2

Frequencies

GnomAD3 genomes AF: 0.0998 AC: 15170 AN: 152044 Hom.: 1995 Cov.: 32

Gnomad AFR AF: 0.188

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0941

Gnomad ASJ AF: 0.0392

Gnomad EAS AF: 0.634

Gnomad SAS AF: 0.162

Gnomad FIN AF: 0.0850

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.00994

Gnomad OTH AF: 0.0852

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

GnomAD4 genome AF: 0.0999 AC: 15200 AN: 152162 Hom.: 2002 Cov.: 32 AF XY: 0.107 AC XY: 7973 AN XY: 74402

Gnomad4 AFR AF: 0.188

Gnomad4 AMR AF: 0.0944

Gnomad4 ASJ AF: 0.0392

Gnomad4 EAS AF: 0.634

Gnomad4 SAS AF: 0.162

Gnomad4 FIN AF: 0.0850

Gnomad4 NFE AF: 0.00991

Gnomad4 OTH AF: 0.0923

Alfa AF: 0.0292 Hom.: 130

Bravo AF: 0.108

Asia WGS AF: 0.372 AC: 1293 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.4
DANN	Benign	0.64

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: rs9332624; hg19: chr1-169497926;