rs2239852

Variant names:

• chr1-169543286-C-T
• rs2239852
• NM_000130.5:c.1976-172G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-169543286-C-T
• chr1-169543286-C-G

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.1976-172G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.396 in 151,896 control chromosomes in the GnomAD database, including 12,903 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.40 (12903 hom., cov: 32)
• Consequence: F5 NM_000130.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.854
• Publications: 7 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: Genomics England PanelApp, ClinGen, Labcorp Genetics (formerly Invitae)
• 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=-0.92).
• BP6: Variant 1-169543286-C-T is Benign according to our data. Variant chr1-169543286-C-T is described in ClinVar as Benign. ClinVar VariationId is 1254957.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.875 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	F5	NM_000130.5	MANE Select	c.1976-172G>A		intron	N/A	NP_000121.2	P12259

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	F5	ENST00000367797.9	TSL:1 MANE Select	c.1976-172G>A		intron	N/A	ENSP00000356771.3	P12259
	F5	ENST00000367796.3	TSL:5	c.1991-172G>A		intron	N/A	ENSP00000356770.3	A0A0A0MRJ7
	F5	ENST00000904428.1		c.1611+6515G>A		intron	N/A	ENSP00000574487.1

Frequencies

GnomAD3 genomes AF: 0.395 AC: 59996 AN: 151778 Hom.: 12871 Cov.: 32

Gnomad AFR AF: 0.365

Gnomad AMI AF: 0.194

Gnomad AMR AF: 0.538

Gnomad ASJ AF: 0.282

Gnomad EAS AF: 0.897

Gnomad SAS AF: 0.558

Gnomad FIN AF: 0.378

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.343

Gnomad OTH AF: 0.411

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

GnomAD4 genome AF: 0.396 AC: 60079 AN: 151896 Hom.: 12903 Cov.: 32 AF XY: 0.407 AC XY: 30199 AN XY: 74216

African (AFR) AF: 0.366 AC: 15137 AN: 41410

American (AMR) AF: 0.539 AC: 8218 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.282 AC: 979 AN: 3466

East Asian (EAS) AF: 0.897 AC: 4644 AN: 5180

South Asian (SAS) AF: 0.558 AC: 2684 AN: 4812

European-Finnish (FIN) AF: 0.378 AC: 3972 AN: 10516

Middle Eastern (MID) AF: 0.344 AC: 101 AN: 294

European-Non Finnish (NFE) AF: 0.343 AC: 23291 AN: 67946

Other (OTH) AF: 0.416 AC: 876 AN: 2108

Alfa AF: 0.366 Hom.: 14785

Bravo AF: 0.407

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.26
DANN	Benign	0.62
PhyloP100		-0.85
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2239852; hg19: chr1-169512524;