chr1-169519689-C-T

Variant names:

• chr1-169519689-C-T
• rs3766103
• NM_000130.5:c.6193+831G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 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 -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 VariationId 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 rank	MANE	Protein	UniProt
F5	NM_000130.5	c.6193+831G>A		intron_variant	Intron 22 of 24	ENST00000367797.9	NP_000121.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
F5	ENST00000367797.9	c.6193+831G>A		intron_variant	Intron 22 of 24	1	NM_000130.5	ENSP00000356771.3
F5	ENST00000367796.3	c.6208+831G>A		intron_variant	Intron 22 of 24	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

African (AFR) AF: 0.419 AC: 17362 AN: 41444

American (AMR) AF: 0.402 AC: 6137 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.483 AC: 1675 AN: 3470

East Asian (EAS) AF: 0.675 AC: 3489 AN: 5170

South Asian (SAS) AF: 0.438 AC: 2106 AN: 4812

European-Finnish (FIN) AF: 0.613 AC: 6471 AN: 10562

Middle Eastern (MID) AF: 0.415 AC: 122 AN: 294

European-Non Finnish (NFE) AF: 0.536 AC: 36444 AN: 67964

Other (OTH) AF: 0.480 AC: 1014 AN: 2112

Alfa AF: 0.508 Hom.: 28310

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

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.21
DANN	Benign	0.36
PhyloP100		-1.8
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: rs3766103; hg19: chr1-169488927;