rs6703865

chr1-169581725-G-A

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
F5	NM_000130.5	c.250+706C>T		intron_variant		ENST00000367797.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
F5	ENST00000367797.9	c.250+706C>T		intron_variant		1	NM_000130.5	P2
F5	ENST00000367796.3	c.250+706C>T		intron_variant		5		A2

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

Gnomad4 AFR AF: 0.174

Gnomad4 AMR AF: 0.0787

Gnomad4 ASJ AF: 0.107

Gnomad4 EAS AF: 0.00772

Gnomad4 SAS AF: 0.0340

Gnomad4 FIN AF: 0.0376

Gnomad4 NFE AF: 0.0871

Gnomad4 OTH AF: 0.103

Alfa AF: 0.0893 Hom.: 406

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs6703865; hg19: chr1-169550963;