rs6031

Positions:

chr1-169542665-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000130.5(F5):c.2425C>T(p.Pro809Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00429 in 1,614,062 control chromosomes in the GnomAD database, including 263 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. P809P) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.023 ( 127 hom., cov: 32)

Exomes 𝑓: 0.0024 ( 136 hom. )

Consequence

F5
NM_000130.5 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 1.86

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0029233396).

BP6

Variant 1-169542665-G-A is Benign according to our data. Variant chr1-169542665-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 255198.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.077 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
F5	NM_000130.5 linkuse as main transcript	c.2425C>T	p.Pro809Ser	missense_variant	13/25	ENST00000367797.9	NP_000121.2	P12259

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
F5	ENST00000367797.9 linkuse as main transcript	c.2425C>T	p.Pro809Ser	missense_variant	13/25	1	NM_000130.5	ENSP00000356771.3		P12259
F5	ENST00000367796.3 linkuse as main transcript	c.2440C>T	p.Pro814Ser	missense_variant	13/25	5		ENSP00000356770.3		A0A0A0MRJ7

Frequencies

GnomAD3 genomes

AF:

0.0226

AC:

3437

AN:

152122

Hom.:

127

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0794

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00714

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000250

Gnomad OTH

AF:

0.0101

GnomAD3 exomes

AF:

0.00629

AC:

1580

AN:

251316

Hom.:

AF XY:

0.00454

AC XY:

617

AN XY:

135830

show subpopulations

Gnomad AFR exome

AF:

0.0845

Gnomad AMR exome

AF:

0.00440

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000273

Gnomad OTH exome

AF:

0.00358

GnomAD4 exome

AF:

0.00239

AC:

3489

AN:

1461822

Hom.:

136

Cov.:

AF XY:

0.00208

AC XY:

1510

AN XY:

727214

show subpopulations

Gnomad4 AFR exome

AF:

0.0825

Gnomad4 AMR exome

AF:

0.00490

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000133

Gnomad4 OTH exome

AF:

0.00536

GnomAD4 genome

AF:

0.0226

AC:

3441

AN:

152240

Hom.:

127

Cov.:

AF XY:

0.0220

AC XY:

1635

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.0793

Gnomad4 AMR

AF:

0.00713

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000250

Gnomad4 OTH

AF:

0.00995

Alfa

AF:

0.00515

Hom.:

Bravo

AF:

0.0261

ESP6500AA

AF:

0.0797

AC:

351

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.00790

AC:

959

Asia WGS

AF:

0.00462

AC:

AN:

3476

EpiCase

AF:

0.000273

EpiControl

AF:

0.000830

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 05, 2021	- -

Thrombophilia due to activated protein C resistance

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -
Likely benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Congenital factor V deficiency

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Budd-Chiari syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

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

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

Thrombophilia due to thrombin defect

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.095

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.71

CADD

Benign

2.9

DANN

Benign

0.90

DEOGEN2

Benign

0.10

T;T

Eigen

Benign

-0.51

Eigen_PC

Benign

-0.52

FATHMM_MKL

Benign

0.16

LIST_S2

Benign

0.40

T;T

MetaRNN

Benign

0.0029

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.6

L;.

PrimateAI

Benign

0.17

PROVEAN

Benign

-2.2

N;N

REVEL

Benign

0.094

Sift

Benign

0.24

T;T

Sift4G

Benign

0.65

T;T

Polyphen

0.45

P;.

Vest4

0.096

MVP

0.36

MPC

0.090

ClinPred

0.023

GERP RS

5.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.022

gMVP

0.29

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