rs3766119

Positions:

• chr1-169561743-C-A
• chr1-169561743-C-G
• chr1-169561743-C-T

Variant summary

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

The NM_000130.5(F5):​c.374-977G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.241 in 151,882 control chromosomes in the GnomAD database, including 5,334 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 0.24 (5334 hom., cov: 32)
• Consequence: F5 NM_000130.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0950

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=-0.94).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.347 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
F5	NM_000130.5	c.374-977G>T		intron_variant		ENST00000367797.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
F5	ENST00000367797.9	c.374-977G>T		intron_variant		1	NM_000130.5	P2
F5	ENST00000367796.3	c.374-977G>T		intron_variant		5		A2

Frequencies

GnomAD3 genomes AF: 0.241 AC: 36649 AN: 151764 Hom.: 5321 Cov.: 32

Gnomad AFR AF: 0.0711

Gnomad AMI AF: 0.152

Gnomad AMR AF: 0.328

Gnomad ASJ AF: 0.264

Gnomad EAS AF: 0.219

Gnomad SAS AF: 0.360

Gnomad FIN AF: 0.368

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.299

Gnomad OTH AF: 0.256

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

GnomAD4 genome AF: 0.241 AC: 36666 AN: 151882 Hom.: 5334 Cov.: 32 AF XY: 0.247 AC XY: 18331 AN XY: 74188

Gnomad4 AFR AF: 0.0709

Gnomad4 AMR AF: 0.329

Gnomad4 ASJ AF: 0.264

Gnomad4 EAS AF: 0.220

Gnomad4 SAS AF: 0.361

Gnomad4 FIN AF: 0.368

Gnomad4 NFE AF: 0.299

Gnomad4 OTH AF: 0.251

Alfa AF: 0.266 Hom.: 2700

Bravo AF: 0.232

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.3
DANN	Benign	0.32

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: rs3766119; hg19: chr1-169530981;