chr1-169552611-T-C

Variant names:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000130.5(F5):c.1242A>G(p.Lys414Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0839 in 1,613,148 control chromosomes in the GnomAD database, including 5,881 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.086 ( 606 hom., cov: 32)

Exomes 𝑓: 0.084 ( 5275 hom. )

Consequence

F5
NM_000130.5 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.122

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 1-169552611-T-C is Benign according to our data. Variant chr1-169552611-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 255189.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.122 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0919 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
F5	NM_000130.5 link	c.1242A>G	p.Lys414Lys	synonymous_variant	Exon 8 of 25	ENST00000367797.9	NP_000121.2	P12259

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
F5	ENST00000367797.9 link	c.1242A>G	p.Lys414Lys	synonymous_variant	Exon 8 of 25	1	NM_000130.5	ENSP00000356771.3		P12259
F5	ENST00000367796.3 link	c.1242A>G	p.Lys414Lys	synonymous_variant	Exon 8 of 25	5		ENSP00000356770.3		A0A0A0MRJ7

Frequencies

GnomAD3 genomes

AF:

0.0863

AC:

13124

AN:

152140

Hom.:

607

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0945

Gnomad AMI

AF:

0.0592

Gnomad AMR

AF:

0.0955

Gnomad ASJ

AF:

0.157

Gnomad EAS

AF:

0.0604

Gnomad SAS

AF:

0.0942

Gnomad FIN

AF:

0.0573

Gnomad MID

AF:

0.0886

Gnomad NFE

AF:

0.0817

Gnomad OTH

AF:

0.0900

GnomAD3 exomes

AF:

0.0877

AC:

22041

AN:

251372

Hom.:

1034

AF XY:

0.0875

AC XY:

11886

AN XY:

135850

show subpopulations

Gnomad AFR exome

AF:

0.0939

Gnomad AMR exome

AF:

0.101

Gnomad ASJ exome

AF:

0.160

Gnomad EAS exome

AF:

0.0636

Gnomad SAS exome

AF:

0.100

Gnomad FIN exome

AF:

0.0576

Gnomad NFE exome

AF:

0.0826

Gnomad OTH exome

AF:

0.0856

GnomAD4 exome

AF:

0.0836

AC:

122170

AN:

1460890

Hom.:

5275

Cov.:

AF XY:

0.0844

AC XY:

61319

AN XY:

726772

show subpopulations

Gnomad4 AFR exome

AF:

0.0945

Gnomad4 AMR exome

AF:

0.102

Gnomad4 ASJ exome

AF:

0.151

Gnomad4 EAS exome

AF:

0.0595

Gnomad4 SAS exome

AF:

0.101

Gnomad4 FIN exome

AF:

0.0581

Gnomad4 NFE exome

AF:

0.0815

Gnomad4 OTH exome

AF:

0.0882

GnomAD4 genome

AF:

0.0862

AC:

13127

AN:

152258

Hom.:

606

Cov.:

AF XY:

0.0837

AC XY:

6235

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.0944

Gnomad4 AMR

AF:

0.0952

Gnomad4 ASJ

AF:

0.157

Gnomad4 EAS

AF:

0.0607

Gnomad4 SAS

AF:

0.0939

Gnomad4 FIN

AF:

0.0573

Gnomad4 NFE

AF:

0.0817

Gnomad4 OTH

AF:

0.0914

Alfa

AF:

0.0896

Hom.:

795

Bravo

AF:

0.0877

Asia WGS

AF:

0.103

AC:

358

AN:

3476

EpiCase

AF:

0.0922

EpiControl

AF:

0.0906

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 27884173, 16542711, 20981092) -

Feb 01, 2017

CeGaT Center for Human Genetics Tuebingen

Significance: Likely 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

- -

Thrombophilia due to activated protein C resistance

Benign:1

Apr 27, 2017

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

5.4

DANN

Benign

0.65

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over