1-169528493-T-G

Variant names:

• chr1-169528493-T-G
• rs9332628
• NM_000130.5:c.5420-399A>C

Variant summary

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

The NM_000130.5(F5):​c.5420-399A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0858 in 152,236 control chromosomes in the GnomAD database, including 1,665 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 0.086 (1665 hom., cov: 32)
• Consequence: F5 NM_000130.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.877
• Publications: 1 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.613 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
F5	NM_000130.5	c.5420-399A>C		intron_variant	Intron 16 of 24	ENST00000367797.9	NP_000121.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
F5	ENST00000367797.9	c.5420-399A>C		intron_variant	Intron 16 of 24	1	NM_000130.5	ENSP00000356771.3
F5	ENST00000367796.3	c.5435-399A>C		intron_variant	Intron 16 of 24	5		ENSP00000356770.3

Frequencies

GnomAD3 genomes AF: 0.0858 AC: 13047 AN: 152118 Hom.: 1661 Cov.: 32

Gnomad AFR AF: 0.139

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0897

Gnomad ASJ AF: 0.0392

Gnomad EAS AF: 0.631

Gnomad SAS AF: 0.161

Gnomad FIN AF: 0.0858

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.00979

Gnomad OTH AF: 0.0738

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

GnomAD4 genome AF: 0.0858 AC: 13067 AN: 152236 Hom.: 1665 Cov.: 32 AF XY: 0.0933 AC XY: 6945 AN XY: 74440

African (AFR) AF: 0.139 AC: 5766 AN: 41530

American (AMR) AF: 0.0900 AC: 1376 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0392 AC: 136 AN: 3470

East Asian (EAS) AF: 0.631 AC: 3261 AN: 5168

South Asian (SAS) AF: 0.161 AC: 775 AN: 4828

European-Finnish (FIN) AF: 0.0858 AC: 910 AN: 10608

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.00978 AC: 665 AN: 68028

Other (OTH) AF: 0.0806 AC: 170 AN: 2110

Alfa AF: 0.0307 Hom.: 539

Bravo AF: 0.0920

Asia WGS AF: 0.369 AC: 1282 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.21
DANN	Benign	0.50
PhyloP100		-0.88
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: rs9332628; hg19: chr1-169497731;