rs6678795

Variant names:

• chr1-169564028-G-A
• rs6678795
• NM_000130.5:c.374-3262C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-169564028-G-A
• chr1-169564028-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.374-3262C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.596 in 151,936 control chromosomes in the GnomAD database, including 28,442 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 0.60 (28442 hom., cov: 32)
• Consequence: F5 NM_000130.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.32
• Publications: 13 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=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.85 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
F5	NM_000130.5	c.374-3262C>T		intron_variant	Intron 3 of 24	ENST00000367797.9	NP_000121.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
F5	ENST00000367797.9	c.374-3262C>T		intron_variant	Intron 3 of 24	1	NM_000130.5	ENSP00000356771.3
F5	ENST00000367796.3	c.374-3262C>T		intron_variant	Intron 3 of 24	5		ENSP00000356770.3

Frequencies

GnomAD3 genomes AF: 0.596 AC: 90486 AN: 151818 Hom.: 28397 Cov.: 32

Gnomad AFR AF: 0.761

Gnomad AMI AF: 0.240

Gnomad AMR AF: 0.637

Gnomad ASJ AF: 0.471

Gnomad EAS AF: 0.872

Gnomad SAS AF: 0.555

Gnomad FIN AF: 0.624

Gnomad MID AF: 0.405

Gnomad NFE AF: 0.476

Gnomad OTH AF: 0.578

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

GnomAD4 genome AF: 0.596 AC: 90595 AN: 151936 Hom.: 28442 Cov.: 32 AF XY: 0.604 AC XY: 44827 AN XY: 74272

African (AFR) AF: 0.762 AC: 31587 AN: 41474

American (AMR) AF: 0.638 AC: 9727 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.471 AC: 1634 AN: 3470

East Asian (EAS) AF: 0.872 AC: 4493 AN: 5154

South Asian (SAS) AF: 0.555 AC: 2669 AN: 4810

European-Finnish (FIN) AF: 0.624 AC: 6599 AN: 10582

Middle Eastern (MID) AF: 0.412 AC: 121 AN: 294

European-Non Finnish (NFE) AF: 0.476 AC: 32320 AN: 67872

Other (OTH) AF: 0.580 AC: 1226 AN: 2112

Alfa AF: 0.503 Hom.: 34153

Bravo AF: 0.609

Asia WGS AF: 0.732 AC: 2547 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.48
DANN	Benign	0.61
PhyloP100		-1.3
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: rs6678795; hg19: chr1-169533266;