rs2269648

Variant names:

• chr1-169586812-C-T
• rs2269648
• ENST00000367796.3:c.-426G>A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000367796.3(F5):​c.-426G>A variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.3 in 152,074 control chromosomes in the GnomAD database, including 8,580 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.30 (8580 hom., cov: 32)
• Consequence: F5 ENST00000367796.3 upstream_gene
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0850

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 1-169586812-C-T is Benign according to our data. Variant chr1-169586812-C-T is described in ClinVar as [Benign]. Clinvar id is 1232860.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.635 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
F5	ENST00000367796.3	c.-426G>A		upstream_gene_variant		5		ENSP00000356770.3

Frequencies

GnomAD3 genomes AF: 0.299 AC: 45501 AN: 151958 Hom.: 8561 Cov.: 32

Gnomad AFR AF: 0.493

Gnomad AMI AF: 0.0877

Gnomad AMR AF: 0.285

Gnomad ASJ AF: 0.205

Gnomad EAS AF: 0.654

Gnomad SAS AF: 0.196

Gnomad FIN AF: 0.253

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.182

Gnomad OTH AF: 0.280

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

GnomAD4 genome AF: 0.300 AC: 45549 AN: 152074 Hom.: 8580 Cov.: 32 AF XY: 0.302 AC XY: 22465 AN XY: 74346

Gnomad4 AFR AF: 0.493

Gnomad4 AMR AF: 0.284

Gnomad4 ASJ AF: 0.205

Gnomad4 EAS AF: 0.653

Gnomad4 SAS AF: 0.195

Gnomad4 FIN AF: 0.253

Gnomad4 NFE AF: 0.182

Gnomad4 OTH AF: 0.282

Alfa AF: 0.246 Hom.: 1838

Bravo AF: 0.313

Asia WGS AF: 0.445 AC: 1546 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Nov 10, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.6
DANN	Benign	0.57

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2269648; hg19: chr1-169556050;