rs6019

Positions:

Variant summary

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

The NM_000130.5(F5):c.319G>C(p.Asp107His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0676 in 1,612,870 control chromosomes in the GnomAD database, including 7,268 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.13 ( 2680 hom., cov: 32)

Exomes 𝑓: 0.061 ( 4588 hom. )

Consequence

F5
NM_000130.5 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.813

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=0.0040112734).

BP6

Variant 1-169572275-C-G is Benign according to our data. Variant chr1-169572275-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 255203.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.341 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.319G>C	p.Asp107His	missense_variant	3/25	ENST00000367797.9	NP_000121.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
F5	ENST00000367797.9 linkuse as main transcript	c.319G>C	p.Asp107His	missense_variant	3/25	1	NM_000130.5	ENSP00000356771	P2
F5	ENST00000367796.3 linkuse as main transcript	c.319G>C	p.Asp107His	missense_variant	3/25	5		ENSP00000356770	A2

Frequencies

GnomAD3 genomes

AF:

0.131

AC:

19982

AN:

151980

Hom.:

2676

Cov.:

show subpopulations

Gnomad AFR

AF:

0.347

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.0683

Gnomad ASJ

AF:

0.0455

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.0137

Gnomad FIN

AF:

0.0234

Gnomad MID

AF:

0.0669

Gnomad NFE

AF:

0.0574

Gnomad OTH

AF:

0.0989

GnomAD3 exomes

AF:

0.0623

AC:

15617

AN:

250658

Hom.:

1356

AF XY:

0.0554

AC XY:

7507

AN XY:

135508

show subpopulations

Gnomad AFR exome

AF:

0.356

Gnomad AMR exome

AF:

0.0488

Gnomad ASJ exome

AF:

0.0534

Gnomad EAS exome

AF:

0.000436

Gnomad SAS exome

AF:

0.0131

Gnomad FIN exome

AF:

0.0255

Gnomad NFE exome

AF:

0.0554

Gnomad OTH exome

AF:

0.0641

GnomAD4 exome

AF:

0.0610

AC:

89113

AN:

1460772

Hom.:

4588

Cov.:

AF XY:

0.0585

AC XY:

42500

AN XY:

726700

show subpopulations

Gnomad4 AFR exome

AF:

0.357

Gnomad4 AMR exome

AF:

0.0524

Gnomad4 ASJ exome

AF:

0.0541

Gnomad4 EAS exome

AF:

0.000176

Gnomad4 SAS exome

AF:

0.0128

Gnomad4 FIN exome

AF:

0.0283

Gnomad4 NFE exome

AF:

0.0594

Gnomad4 OTH exome

AF:

0.0721

GnomAD4 genome

AF:

0.131

AC:

19990

AN:

152098

Hom.:

2680

Cov.:

AF XY:

0.124

AC XY:

9195

AN XY:

74372

show subpopulations

Gnomad4 AFR

AF:

0.346

Gnomad4 AMR

AF:

0.0681

Gnomad4 ASJ

AF:

0.0455

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.0135

Gnomad4 FIN

AF:

0.0234

Gnomad4 NFE

AF:

0.0574

Gnomad4 OTH

AF:

0.0979

Alfa

AF:

0.0676

Hom.:

451

Bravo

AF:

0.145

TwinsUK

AF:

0.0609

AC:

226

ALSPAC

AF:

0.0573

AC:

221

ESP6500AA

AF:

0.342

AC:

1506

ESP6500EA

AF:

0.0548

AC:

471

ExAC

AF:

0.0685

AC:

8319

Asia WGS

AF:

0.0280

AC:

AN:

3478

EpiCase

AF:

0.0575

EpiControl

AF:

0.0570

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

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 04, 2021	This variant is associated with the following publications: (PMID: 23662219, 12651267, 19020903, 22044617) -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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

Feb 01, 2024

- -

Budd-Chiari syndrome

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Apr 27, 2017

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. -

Factor V deficiency

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Apr 27, 2017

Thrombophilia due to thrombin defect

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Apr 27, 2017

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.18

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Uncertain

0.60

D;T

Eigen

Benign

-0.14

Eigen_PC

Benign

-0.021

FATHMM_MKL

Benign

0.29

LIST_S2

Benign

0.31

T;T

MetaRNN

Benign

0.0040

T;T

MetaSVM

Uncertain

0.59

MutationAssessor

Uncertain

2.1

M;.

MutationTaster

Benign

0.57

P;P;P

PrimateAI

Benign

0.29

PROVEAN

Uncertain

-3.8

D;D

REVEL

Uncertain

0.33

Sift

Benign

0.14

T;T

Sift4G

Benign

0.13

T;T

Polyphen

0.063

B;.

Vest4

0.11

MPC

0.13

ClinPred

0.019

GERP RS

3.2

Varity_R

0.16

gMVP

0.62

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