rs9332575

Positions:

• chr1-169557863-T-C

Variant summary

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

The ENST00000367797.9(F5):​c.731-996A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0758 in 152,140 control chromosomes in the GnomAD database, including 604 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 0.076 (604 hom., cov: 31)
• Consequence: F5 ENST00000367797.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.86

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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.105 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
F5	NM_000130.5	c.731-996A>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.731-996A>G		intron_variant		1	NM_000130.5	ENSP00000356771	P2
F5	ENST00000367796.3	c.731-996A>G		intron_variant		5		ENSP00000356770	A2

Frequencies

GnomAD3 genomes AF: 0.0758 AC: 11522 AN: 152022 Hom.: 599 Cov.: 31

Gnomad AFR AF: 0.0203

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.0963

Gnomad ASJ AF: 0.0620

Gnomad EAS AF: 0.00193

Gnomad SAS AF: 0.0375

Gnomad FIN AF: 0.124

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.107

Gnomad OTH AF: 0.0809

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

GnomAD4 genome AF: 0.0758 AC: 11534 AN: 152140 Hom.: 604 Cov.: 31 AF XY: 0.0752 AC XY: 5592 AN XY: 74376

Gnomad4 AFR AF: 0.0203

Gnomad4 AMR AF: 0.0971

Gnomad4 ASJ AF: 0.0620

Gnomad4 EAS AF: 0.00193

Gnomad4 SAS AF: 0.0377

Gnomad4 FIN AF: 0.124

Gnomad4 NFE AF: 0.107

Gnomad4 OTH AF: 0.0791

Alfa AF: 0.0909 Hom.: 95

Bravo AF: 0.0739

Asia WGS AF: 0.0200 AC: 71 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.6
DANN	Benign	0.73

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: rs9332575; hg19: chr1-169527101;