rs2213865

Variant names:

• chr1-169516890-G-A
• rs2213865
• NM_000130.5:c.6346-1264C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-169516890-G-A
• chr1-169516890-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000130.5(F5):​c.6346-1264C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0885 in 152,076 control chromosomes in the GnomAD database, including 707 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 0.088 (707 hom., cov: 32)
• Consequence: F5 NM_000130.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.344
• Publications: 10 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.131 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
F5	NM_000130.5	c.6346-1264C>T		intron_variant	Intron 23 of 24	ENST00000367797.9	NP_000121.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
F5	ENST00000367797.9	c.6346-1264C>T		intron_variant	Intron 23 of 24	1	NM_000130.5	ENSP00000356771.3
F5	ENST00000367796.3	c.6361-1264C>T		intron_variant	Intron 23 of 24	5		ENSP00000356770.3

Frequencies

GnomAD3 genomes AF: 0.0885 AC: 13441 AN: 151960 Hom.: 707 Cov.: 32

Gnomad AFR AF: 0.134

Gnomad AMI AF: 0.0373

Gnomad AMR AF: 0.0913

Gnomad ASJ AF: 0.152

Gnomad EAS AF: 0.0604

Gnomad SAS AF: 0.0933

Gnomad FIN AF: 0.0467

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0659

Gnomad OTH AF: 0.0929

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

GnomAD4 genome AF: 0.0885 AC: 13452 AN: 152076 Hom.: 707 Cov.: 32 AF XY: 0.0871 AC XY: 6475 AN XY: 74344

African (AFR) AF: 0.134 AC: 5545 AN: 41492

American (AMR) AF: 0.0909 AC: 1389 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.152 AC: 526 AN: 3468

East Asian (EAS) AF: 0.0605 AC: 313 AN: 5174

South Asian (SAS) AF: 0.0928 AC: 447 AN: 4818

European-Finnish (FIN) AF: 0.0467 AC: 494 AN: 10568

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.0658 AC: 4474 AN: 67964

Other (OTH) AF: 0.0943 AC: 199 AN: 2110

Alfa AF: 0.0693 Hom.: 354

Bravo AF: 0.0912

Asia WGS AF: 0.0970 AC: 339 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.22
DANN	Benign	0.69
PhyloP100		-0.34
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: rs2213865; hg19: chr1-169486128;