rs9332683

Positions:

• chr1-169584151-A-G
• chr1-169584151-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_000130.5(F5):​c.159-1629T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00607 in 152,346 control chromosomes in the GnomAD database, including 3 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 0.0061 (3 hom., cov: 33)
• Consequence: F5 NM_000130.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.273

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=-0.9).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00607 (925/152346) while in subpopulation NFE AF= 0.0103 (703/68030). AF 95% confidence interval is 0.0097. There are 3 homozygotes in gnomad4. There are 410 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 3 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
F5	NM_000130.5	c.159-1629T>C		intron_variant		ENST00000367797.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
F5	ENST00000367797.9	c.159-1629T>C		intron_variant		1	NM_000130.5	P2
F5	ENST00000367796.3	c.159-1629T>C		intron_variant		5		A2

Frequencies

GnomAD3 genomes AF: 0.00608 AC: 925 AN: 152228 Hom.: 3 Cov.: 33

Gnomad AFR AF: 0.00234

Gnomad AMI AF: 0.0154

Gnomad AMR AF: 0.00320

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00331

Gnomad FIN AF: 0.00348

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0103

Gnomad OTH AF: 0.00335

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

GnomAD4 genome AF: 0.00607 AC: 925 AN: 152346 Hom.: 3 Cov.: 33 AF XY: 0.00550 AC XY: 410 AN XY: 74504

Gnomad4 AFR AF: 0.00233

Gnomad4 AMR AF: 0.00320

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.000192

Gnomad4 SAS AF: 0.00332

Gnomad4 FIN AF: 0.00348

Gnomad4 NFE AF: 0.0103

Gnomad4 OTH AF: 0.00331

Alfa AF: 0.00288 Hom.: 1

Bravo AF: 0.00625

Asia WGS AF: 0.00318 AC: 11 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.5
DANN	Benign	0.67

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: rs9332683; hg19: chr1-169553389;