rs6427203

Variant names:

• chr1-169559793-A-C
• rs6427203
• NM_000130.5:c.587-497T>G

Your query was ambiguous. Multiple possible variants found:

• chr1-169559793-A-C
• chr1-169559793-A-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.587-497T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.323 in 152,016 control chromosomes in the GnomAD database, including 10,504 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 0.32 (10504 hom., cov: 32)
• Consequence: F5 NM_000130.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.75
• Publications: 5 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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.634 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
F5	NM_000130.5	c.587-497T>G		intron_variant	Intron 4 of 24	ENST00000367797.9	NP_000121.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
F5	ENST00000367797.9	c.587-497T>G		intron_variant	Intron 4 of 24	1	NM_000130.5	ENSP00000356771.3
F5	ENST00000367796.3	c.587-497T>G		intron_variant	Intron 4 of 24	5		ENSP00000356770.3

Frequencies

GnomAD3 genomes AF: 0.322 AC: 48957 AN: 151898 Hom.: 10481 Cov.: 32

Gnomad AFR AF: 0.582

Gnomad AMI AF: 0.0877

Gnomad AMR AF: 0.292

Gnomad ASJ AF: 0.205

Gnomad EAS AF: 0.653

Gnomad SAS AF: 0.194

Gnomad FIN AF: 0.255

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.177

Gnomad OTH AF: 0.298

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

GnomAD4 genome AF: 0.323 AC: 49027 AN: 152016 Hom.: 10504 Cov.: 32 AF XY: 0.324 AC XY: 24110 AN XY: 74326

African (AFR) AF: 0.582 AC: 24115 AN: 41424

American (AMR) AF: 0.291 AC: 4445 AN: 15268

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

East Asian (EAS) AF: 0.652 AC: 3357 AN: 5148

South Asian (SAS) AF: 0.193 AC: 934 AN: 4828

European-Finnish (FIN) AF: 0.255 AC: 2698 AN: 10594

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.177 AC: 11999 AN: 67978

Other (OTH) AF: 0.304 AC: 639 AN: 2100

Alfa AF: 0.248 Hom.: 1615

Bravo AF: 0.340

Asia WGS AF: 0.450 AC: 1563 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	7.4
DANN	Benign	0.72
PhyloP100		2.8
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: rs6427203; hg19: chr1-169529031;