1-169529596-T-C

Variant names:

• chr1-169529596-T-C
• rs6009
• NM_000130.5:c.5419+12A>G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000130.5(F5):​c.5419+12A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.936 in 1,610,466 control chromosomes in the GnomAD database, including 705,925 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.93 (65297 hom., cov: 31)
  • Exomes 𝑓: 0.94 (640628 hom.)
• Consequence: F5 NM_000130.5 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:10
• Conservation: PhyloP100: 0.348

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP6: Variant 1-169529596-T-C is Benign according to our data. Variant chr1-169529596-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 255211.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-169529596-T-C is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
F5	NM_000130.5	c.5419+12A>G		intron_variant	Intron 16 of 24	ENST00000367797.9	NP_000121.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
F5	ENST00000367797.9	c.5419+12A>G		intron_variant	Intron 16 of 24	1	NM_000130.5	ENSP00000356771.3
F5	ENST00000367796.3	c.5434+12A>G		intron_variant	Intron 16 of 24	5		ENSP00000356770.3

Frequencies

GnomAD3 genomes AF: 0.926 AC: 140819 AN: 152078 Hom.: 65245 Cov.: 31

Gnomad AFR AF: 0.895

Gnomad AMI AF: 0.893

Gnomad AMR AF: 0.950

Gnomad ASJ AF: 0.876

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.934

Gnomad FIN AF: 0.950

Gnomad MID AF: 0.851

Gnomad NFE AF: 0.933

Gnomad OTH AF: 0.925

GnomAD3 exomes AF: 0.937 AC: 234759 AN: 250570 Hom.: 110130 AF XY: 0.935 AC XY: 126629 AN XY: 135458

Gnomad AFR exome AF: 0.895

Gnomad AMR exome AF: 0.968

Gnomad ASJ exome AF: 0.881

Gnomad EAS exome AF: 0.999

Gnomad SAS exome AF: 0.930

Gnomad FIN exome AF: 0.949

Gnomad NFE exome AF: 0.928

Gnomad OTH exome AF: 0.937

GnomAD4 exome AF: 0.937 AC: 1366487 AN: 1458270 Hom.: 640628 Cov.: 33 AF XY: 0.936 AC XY: 679390 AN XY: 725644

Gnomad4 AFR exome AF: 0.895

Gnomad4 AMR exome AF: 0.966

Gnomad4 ASJ exome AF: 0.882

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.926

Gnomad4 FIN exome AF: 0.949

Gnomad4 NFE exome AF: 0.937

Gnomad4 OTH exome AF: 0.933

GnomAD4 genome AF: 0.926 AC: 140928 AN: 152196 Hom.: 65297 Cov.: 31 AF XY: 0.928 AC XY: 69010 AN XY: 74400

Gnomad4 AFR AF: 0.894

Gnomad4 AMR AF: 0.950

Gnomad4 ASJ AF: 0.876

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.934

Gnomad4 FIN AF: 0.950

Gnomad4 NFE AF: 0.933

Gnomad4 OTH AF: 0.926

Alfa AF: 0.923 Hom.: 12316

Bravo AF: 0.924

Asia WGS AF: 0.970 AC: 3373 AN: 3476

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

-

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

-

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Thrombophilia due to activated protein C resistance Benign:2

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Likely 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

- -

Budd-Chiari syndrome Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Factor V deficiency Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Thrombophilia due to thrombin defect Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	15
DANN	Benign	0.74
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs6009; hg19: chr1-169498834;