rs9332684

Positions:

• chr1-169582297-T-C

Variant summary

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

The NM_000130.5(F5):​c.250+134A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.019 in 518,024 control chromosomes in the GnomAD database, including 147 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 0.020 (45 hom., cov: 32)
  • Exomes 𝑓: 0.019 (102 hom.)
• Consequence: F5 NM_000130.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.24

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=-0.93).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0203 (2782/136858) while in subpopulation NFE AF= 0.0245 (1626/66334). AF 95% confidence interval is 0.0235. There are 45 homozygotes in gnomad4. There are 1376 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 45 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
F5	NM_000130.5	c.250+134A>G		intron_variant		ENST00000367797.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
F5	ENST00000367797.9	c.250+134A>G		intron_variant		1	NM_000130.5	P2
F5	ENST00000367796.3	c.250+134A>G		intron_variant		5		A2

Frequencies

GnomAD3 genomes AF: 0.0203 AC: 2780 AN: 136776 Hom.: 45 Cov.: 32

Gnomad AFR AF: 0.00565

Gnomad AMI AF: 0.0554

Gnomad AMR AF: 0.0236

Gnomad ASJ AF: 0.0401

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00432

Gnomad FIN AF: 0.0370

Gnomad MID AF: 0.0392

Gnomad NFE AF: 0.0245

Gnomad OTH AF: 0.0344

GnomAD4 exome AF: 0.0186 AC: 7071 AN: 381166 Hom.: 102 AF XY: 0.0175 AC XY: 3537 AN XY: 202220

Gnomad4 AFR exome AF: 0.00379

Gnomad4 AMR exome AF: 0.0182

Gnomad4 ASJ exome AF: 0.0377

Gnomad4 EAS exome AF: 0.0000755

Gnomad4 SAS exome AF: 0.00405

Gnomad4 FIN exome AF: 0.0342

Gnomad4 NFE exome AF: 0.0202

Gnomad4 OTH exome AF: 0.0205

GnomAD4 genome AF: 0.0203 AC: 2782 AN: 136858 Hom.: 45 Cov.: 32 AF XY: 0.0206 AC XY: 1376 AN XY: 66756

Gnomad4 AFR AF: 0.00563

Gnomad4 AMR AF: 0.0235

Gnomad4 ASJ AF: 0.0401

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00476

Gnomad4 FIN AF: 0.0370

Gnomad4 NFE AF: 0.0245

Gnomad4 OTH AF: 0.0341

Alfa AF: 0.0216 Hom.: 17

Bravo AF: 0.0174

Asia WGS AF: 0.00404 AC: 14 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.47
DANN	Benign	0.35

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs9332684; hg19: chr1-169551535;