rs3766103

Positions:

• chr1-169519689-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000130.5(F5):​c.6193+831G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.496 in 152,020 control chromosomes in the GnomAD database, including 19,202 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.50 (19202 hom., cov: 32)
• Consequence: F5 NM_000130.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.82

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 1-169519689-C-T is Benign according to our data. Variant chr1-169519689-C-T is described in ClinVar as [Benign]. Clinvar id is 1599739.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.656 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
F5	NM_000130.5	c.6193+831G>A		intron_variant		ENST00000367797.9	NP_000121.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
F5	ENST00000367797.9	c.6193+831G>A		intron_variant		1	NM_000130.5	ENSP00000356771.3
F5	ENST00000367796.3	c.6208+831G>A		intron_variant		5		ENSP00000356770.3

Frequencies

GnomAD3 genomes AF: 0.496 AC: 75401 AN: 151902 Hom.: 19204 Cov.: 32

Gnomad AFR AF: 0.419

Gnomad AMI AF: 0.663

Gnomad AMR AF: 0.402

Gnomad ASJ AF: 0.483

Gnomad EAS AF: 0.675

Gnomad SAS AF: 0.437

Gnomad FIN AF: 0.613

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.536

Gnomad OTH AF: 0.479

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

GnomAD4 genome AF: 0.496 AC: 75425 AN: 152020 Hom.: 19202 Cov.: 32 AF XY: 0.496 AC XY: 36882 AN XY: 74304

Gnomad4 AFR AF: 0.419

Gnomad4 AMR AF: 0.402

Gnomad4 ASJ AF: 0.483

Gnomad4 EAS AF: 0.675

Gnomad4 SAS AF: 0.438

Gnomad4 FIN AF: 0.613

Gnomad4 NFE AF: 0.536

Gnomad4 OTH AF: 0.480

Alfa AF: 0.512 Hom.: 19292

Bravo AF: 0.481

Asia WGS AF: 0.518 AC: 1800 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Congenital factor V deficiency Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.21
DANN	Benign	0.36

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: rs3766103; hg19: chr1-169488927;