1-169553316-G-T

Variant names:

• chr1-169553316-G-T
• rs12120605
• NM_000130.5:c.1119-582C>A

Variant summary

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

The NM_000130.5(F5):​c.1119-582C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0717 in 152,182 control chromosomes in the GnomAD database, including 522 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 0.072 (522 hom., cov: 32)
• Consequence: F5 NM_000130.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00800
• Publications: 8 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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0939 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	F5	NM_000130.5	MANE Select	c.1119-582C>A		intron	N/A	NP_000121.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	F5	ENST00000367797.9	TSL:1 MANE Select	c.1119-582C>A		intron	N/A	ENSP00000356771.3
	F5	ENST00000367796.3	TSL:5	c.1119-582C>A		intron	N/A	ENSP00000356770.3

Frequencies

GnomAD3 genomes AF: 0.0717 AC: 10902 AN: 152062 Hom.: 521 Cov.: 32

Gnomad AFR AF: 0.0392

Gnomad AMI AF: 0.103

Gnomad AMR AF: 0.0446

Gnomad ASJ AF: 0.0769

Gnomad EAS AF: 0.0405

Gnomad SAS AF: 0.101

Gnomad FIN AF: 0.120

Gnomad MID AF: 0.0701

Gnomad NFE AF: 0.0896

Gnomad OTH AF: 0.0731

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

GnomAD4 genome AF: 0.0717 AC: 10910 AN: 152182 Hom.: 522 Cov.: 32 AF XY: 0.0720 AC XY: 5355 AN XY: 74384

African (AFR) AF: 0.0393 AC: 1632 AN: 41540

American (AMR) AF: 0.0446 AC: 681 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0769 AC: 267 AN: 3472

East Asian (EAS) AF: 0.0402 AC: 208 AN: 5172

South Asian (SAS) AF: 0.101 AC: 488 AN: 4816

European-Finnish (FIN) AF: 0.120 AC: 1272 AN: 10574

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.0896 AC: 6093 AN: 68008

Other (OTH) AF: 0.0724 AC: 153 AN: 2114

Alfa AF: 0.0840 Hom.: 1392

Bravo AF: 0.0636

Asia WGS AF: 0.0590 AC: 207 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.8
DANN	Benign	0.61
PhyloP100		-0.0080
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: rs12120605; hg19: chr1-169522554;