rs2269648

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 11 publications found

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]

F5 Gene-Disease associations (from GenCC):

• thrombophilia due to activated protein C resistance

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), Genomics England PanelApp
• congenital factor V deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Orphanet, Labcorp Genetics (formerly Invitae)
• East Texas bleeding disorder

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000367796.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	F5	ENST00000367796.3	TSL:5	c.-426G>A		upstream_gene	N/A	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

African (AFR) AF: 0.493 AC: 20419 AN: 41446

American (AMR) AF: 0.284 AC: 4343 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.205 AC: 711 AN: 3470

East Asian (EAS) AF: 0.653 AC: 3360 AN: 5146

South Asian (SAS) AF: 0.195 AC: 942 AN: 4826

European-Finnish (FIN) AF: 0.253 AC: 2683 AN: 10584

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.182 AC: 12366 AN: 67992

Other (OTH) AF: 0.282 AC: 597 AN: 2114

Alfa AF: 0.247 Hom.: 2296

Bravo AF: 0.313

Asia WGS AF: 0.445 AC: 1546 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.6
DANN	Benign	0.57
PhyloP100		-0.085
PromoterAI		-0.0096	Neutral

Splicing

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

Other links and lift over

dbSNP: rs2269648; hg19: chr1-169556050;