rs2213867

Variant names:

• chr1-169520347-T-C
• rs2213867
• NM_000130.5:c.6193+173A>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.6193+173A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.245 in 152,110 control chromosomes in the GnomAD database, including 4,758 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.24 (4758 hom., cov: 32)
• Consequence: F5 NM_000130.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.06
• 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: 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=-0.82).
• BP6: Variant 1-169520347-T-C is Benign according to our data. Variant chr1-169520347-T-C is described in ClinVar as Benign. ClinVar VariationId is 1224783.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.335 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
F5	NM_000130.5	c.6193+173A>G		intron_variant	Intron 22 of 24	ENST00000367797.9	NP_000121.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
F5	ENST00000367797.9	c.6193+173A>G		intron_variant	Intron 22 of 24	1	NM_000130.5	ENSP00000356771.3
F5	ENST00000367796.3	c.6208+173A>G		intron_variant	Intron 22 of 24	5		ENSP00000356770.3

Frequencies

GnomAD3 genomes AF: 0.245 AC: 37203 AN: 151992 Hom.: 4749 Cov.: 32

Gnomad AFR AF: 0.183

Gnomad AMI AF: 0.191

Gnomad AMR AF: 0.342

Gnomad ASJ AF: 0.167

Gnomad EAS AF: 0.233

Gnomad SAS AF: 0.329

Gnomad FIN AF: 0.205

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.266

Gnomad OTH AF: 0.261

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

GnomAD4 genome AF: 0.245 AC: 37226 AN: 152110 Hom.: 4758 Cov.: 32 AF XY: 0.246 AC XY: 18305 AN XY: 74360

African (AFR) AF: 0.182 AC: 7563 AN: 41508

American (AMR) AF: 0.343 AC: 5241 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.167 AC: 578 AN: 3468

East Asian (EAS) AF: 0.233 AC: 1209 AN: 5180

South Asian (SAS) AF: 0.330 AC: 1589 AN: 4822

European-Finnish (FIN) AF: 0.205 AC: 2170 AN: 10580

Middle Eastern (MID) AF: 0.238 AC: 70 AN: 294

European-Non Finnish (NFE) AF: 0.266 AC: 18082 AN: 67952

Other (OTH) AF: 0.260 AC: 550 AN: 2114

Alfa AF: 0.268 Hom.: 7226

Bravo AF: 0.254

Asia WGS AF: 0.280 AC: 973 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 11, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.4
DANN	Benign	0.56
PhyloP100		1.1
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: rs2213867; hg19: chr1-169489585; COSMIC: COSV63130006; COSMIC: COSV63130006;