NM_000130.5:c.6194-20C>A

Variant names:

• chr1-169518583-G-T
• rs6013
• NM_000130.5:c.6194-20C>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000130.5(F5):​c.6194-20C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0593 in 1,612,548 control chromosomes in the GnomAD database, including 3,314 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.055 (349 hom., cov: 32)
  • Exomes 𝑓: 0.060 (2965 hom.)
• Consequence: F5 NM_000130.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.715
• Publications: 14 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 1-169518583-G-T is Benign according to our data. Variant chr1-169518583-G-T is described in ClinVar as Benign. ClinVar VariationId is 255213.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0966 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000130.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	F5	NM_000130.5	MANE Select	c.6194-20C>A		intron	N/A	NP_000121.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	F5	ENST00000367797.9	TSL:1 MANE Select	c.6194-20C>A		intron	N/A	ENSP00000356771.3
	F5	ENST00000367796.3	TSL:5	c.6209-20C>A		intron	N/A	ENSP00000356770.3

Frequencies

GnomAD3 genomes AF: 0.0554 AC: 8414 AN: 152014 Hom.: 348 Cov.: 32

Gnomad AFR AF: 0.0164

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.101

Gnomad ASJ AF: 0.0750

Gnomad EAS AF: 0.0296

Gnomad SAS AF: 0.0652

Gnomad FIN AF: 0.0859

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0647

Gnomad OTH AF: 0.0647

GnomAD2 exomes AF: 0.0636 AC: 15953 AN: 250670 AF XY: 0.0642

Gnomad AFR exome AF: 0.0139

Gnomad AMR exome AF: 0.0935

Gnomad ASJ exome AF: 0.0698

Gnomad EAS exome AF: 0.0296

Gnomad FIN exome AF: 0.0861

Gnomad NFE exome AF: 0.0609

Gnomad OTH exome AF: 0.0667

GnomAD4 exome AF: 0.0597 AC: 87235 AN: 1460416 Hom.: 2965 Cov.: 31 AF XY: 0.0604 AC XY: 43897 AN XY: 726538

African (AFR) AF: 0.0149 AC: 499 AN: 33440

American (AMR) AF: 0.0940 AC: 4200 AN: 44680

Ashkenazi Jewish (ASJ) AF: 0.0691 AC: 1804 AN: 26106

East Asian (EAS) AF: 0.0594 AC: 2353 AN: 39646

South Asian (SAS) AF: 0.0680 AC: 5865 AN: 86206

European-Finnish (FIN) AF: 0.0841 AC: 4481 AN: 53300

Middle Eastern (MID) AF: 0.0696 AC: 401 AN: 5764

European-Non Finnish (NFE) AF: 0.0577 AC: 64106 AN: 1110956

Other (OTH) AF: 0.0585 AC: 3526 AN: 60318

GnomAD4 genome AF: 0.0554 AC: 8421 AN: 152132 Hom.: 349 Cov.: 32 AF XY: 0.0578 AC XY: 4299 AN XY: 74366

African (AFR) AF: 0.0165 AC: 687 AN: 41526

American (AMR) AF: 0.101 AC: 1540 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0750 AC: 260 AN: 3468

East Asian (EAS) AF: 0.0297 AC: 154 AN: 5182

South Asian (SAS) AF: 0.0651 AC: 313 AN: 4810

European-Finnish (FIN) AF: 0.0859 AC: 908 AN: 10568

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.0647 AC: 4399 AN: 67986

Other (OTH) AF: 0.0640 AC: 135 AN: 2110

Alfa AF: 0.0451 Hom.: 75

Bravo AF: 0.0516

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

May 11, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not specified Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Congenital factor V deficiency Benign:1

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.1
DANN	Benign	0.46
PhyloP100		0.71
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs6013; hg19: chr1-169487821;