rs2187952

Variant names:

• chr1-169512712-G-A
• rs2187952
• NM_000130.5:c.*1601C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000130.5(F5):​c.*1601C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.256 in 151,944 control chromosomes in the GnomAD database, including 5,117 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency: Genomes: 𝑓 0.26 (5117 hom., cov: 32)
• Consequence: F5 NM_000130.5 3_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 0.147
• Publications: 9 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BP6: Variant 1-169512712-G-A is Benign according to our data. Variant chr1-169512712-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 293546.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.338 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000130.5. 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
	F5	NM_000130.5	MANE Select	c.*1601C>T		3_prime_UTR	Exon 25 of 25	NP_000121.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	F5	ENST00000367797.9	TSL:1 MANE Select	c.*1601C>T		3_prime_UTR	Exon 25 of 25	ENSP00000356771.3

Frequencies

GnomAD3 genomes AF: 0.256 AC: 38934 AN: 151826 Hom.: 5107 Cov.: 32

Gnomad AFR AF: 0.225

Gnomad AMI AF: 0.190

Gnomad AMR AF: 0.345

Gnomad ASJ AF: 0.166

Gnomad EAS AF: 0.234

Gnomad SAS AF: 0.329

Gnomad FIN AF: 0.205

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.266

Gnomad OTH AF: 0.269

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

GnomAD4 genome AF: 0.256 AC: 38958 AN: 151944 Hom.: 5117 Cov.: 32 AF XY: 0.257 AC XY: 19100 AN XY: 74250

African (AFR) AF: 0.224 AC: 9297 AN: 41466

American (AMR) AF: 0.346 AC: 5272 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.166 AC: 576 AN: 3464

East Asian (EAS) AF: 0.234 AC: 1208 AN: 5154

South Asian (SAS) AF: 0.330 AC: 1590 AN: 4824

European-Finnish (FIN) AF: 0.205 AC: 2166 AN: 10566

Middle Eastern (MID) AF: 0.245 AC: 72 AN: 294

European-Non Finnish (NFE) AF: 0.266 AC: 18041 AN: 67932

Other (OTH) AF: 0.268 AC: 563 AN: 2100

Alfa AF: 0.267 Hom.: 16061

Bravo AF: 0.267

Asia WGS AF: 0.283 AC: 982 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Thrombophilia due to activated protein C resistance (2)
-	-	1	Budd-Chiari syndrome (1)
-	-	1	Factor V deficiency (1)
-	-	1	not provided (1)
-	-	1	Thrombophilia due to thrombin defect (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	4.1
DANN	Benign	0.43
PhyloP100		0.15

Splicing

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

Other links and lift over

dbSNP: rs2187952; hg19: chr1-169481950;