rs6670678

chr1-169568440-A-Gchr1-169568440-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000130.5(F5):c.373+3781T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.673 in 151,966 control chromosomes in the GnomAD database, including 35,623 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 0.67 (35623 hom., cov: 33)
• Consequence: F5 NM_000130.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.846

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.858 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
F5	NM_000130.5	c.373+3781T>C		intron_variant		ENST00000367797.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
F5	ENST00000367797.9	c.373+3781T>C		intron_variant		1	NM_000130.5	P2
F5	ENST00000367796.3	c.373+3781T>C		intron_variant		5		A2

Frequencies

GnomAD3 genomes AF: 0.673 AC: 102151 AN: 151848 Hom.: 35569 Cov.: 33

Gnomad AFR AF: 0.839

Gnomad AMI AF: 0.361

Gnomad AMR AF: 0.703

Gnomad ASJ AF: 0.587

Gnomad EAS AF: 0.880

Gnomad SAS AF: 0.589

Gnomad FIN AF: 0.661

Gnomad MID AF: 0.545

Gnomad NFE AF: 0.566

Gnomad OTH AF: 0.663

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

GnomAD4 genome AF: 0.673 AC: 102267 AN: 151966 Hom.: 35623 Cov.: 33 AF XY: 0.677 AC XY: 50282 AN XY: 74286

Gnomad4 AFR AF: 0.840

Gnomad4 AMR AF: 0.704

Gnomad4 ASJ AF: 0.587

Gnomad4 EAS AF: 0.880

Gnomad4 SAS AF: 0.589

Gnomad4 FIN AF: 0.661

Gnomad4 NFE AF: 0.566

Gnomad4 OTH AF: 0.663

Alfa AF: 0.636 Hom.: 4023

Bravo AF: 0.688

Asia WGS AF: 0.772 AC: 2678 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.36
Dann	Benign	0.46

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: rs6670678; hg19: chr1-169537678;