1-169581725-G-A

Variant names:

• chr1-169581725-G-A
• rs6703865
• NM_000130.5:c.250+706C>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.250+706C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.103 in 152,162 control chromosomes in the GnomAD database, including 1,020 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 0.10 (1020 hom., cov: 31)
• Consequence: F5 NM_000130.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.499
• Publications: 21 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.17 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
F5	NM_000130.5	c.250+706C>T		intron_variant	Intron 2 of 24	ENST00000367797.9	NP_000121.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
F5	ENST00000367797.9	c.250+706C>T		intron_variant	Intron 2 of 24	1	NM_000130.5	ENSP00000356771.3
F5	ENST00000367796.3	c.250+706C>T		intron_variant	Intron 2 of 24	5		ENSP00000356770.3

Frequencies

GnomAD3 genomes AF: 0.103 AC: 15626 AN: 152044 Hom.: 1011 Cov.: 31

Gnomad AFR AF: 0.173

Gnomad AMI AF: 0.121

Gnomad AMR AF: 0.0789

Gnomad ASJ AF: 0.107

Gnomad EAS AF: 0.00771

Gnomad SAS AF: 0.0339

Gnomad FIN AF: 0.0376

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.0871

Gnomad OTH AF: 0.101

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

GnomAD4 genome AF: 0.103 AC: 15669 AN: 152162 Hom.: 1020 Cov.: 31 AF XY: 0.0998 AC XY: 7423 AN XY: 74406

African (AFR) AF: 0.174 AC: 7203 AN: 41482

American (AMR) AF: 0.0787 AC: 1204 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.107 AC: 373 AN: 3470

East Asian (EAS) AF: 0.00772 AC: 40 AN: 5178

South Asian (SAS) AF: 0.0340 AC: 164 AN: 4830

European-Finnish (FIN) AF: 0.0376 AC: 398 AN: 10598

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.0871 AC: 5924 AN: 68000

Other (OTH) AF: 0.103 AC: 216 AN: 2104

Alfa AF: 0.0930 Hom.: 1603

Bravo AF: 0.110

Asia WGS AF: 0.0450 AC: 159 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.69
DANN	Benign	0.67
PhyloP100		-0.50
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: rs6703865; hg19: chr1-169550963;