rs6003

Positions:

chr1-197061891-C-T

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 2P and 20B. PM1BP4_StrongBP6_Very_StrongBA1

The NM_001994.3(F13B):c.344G>A(p.Arg115His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.883 in 1,612,650 control chromosomes in the GnomAD database, including 638,098 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.77 ( 48909 hom., cov: 30)

Exomes 𝑓: 0.89 ( 589189 hom. )

Consequence

F13B
NM_001994.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6O:1

Conservation

PhyloP100: -0.438

Variant links:

Genes affected

F13B (HGNC:3534): (coagulation factor XIII B chain) This gene encodes coagulation factor XIII B subunit. Coagulation factor XIII is the last zymogen to become activated in the blood coagulation cascade. Plasma factor XIII is a heterotetramer composed of 2 A subunits and 2 B subunits. The A subunits have catalytic function, and the B subunits do not have enzymatic activity and may serve as a plasma carrier molecules. Platelet factor XIII is comprised only of 2 A subunits, which are identical to those of plasma origin. Upon activation by the cleavage of the activation peptide by thrombin and in the presence of calcium ion, the plasma factor XIII dissociates its B subunits and yields the same active enzyme, factor XIIIa, as platelet factor XIII. This enzyme acts as a transglutaminase to catalyze the formation of gamma-glutamyl-epsilon-lysine crosslinking between fibrin molecules, thus stabilizing the fibrin clot. Factor XIII deficiency is classified into two categories: type I deficiency, characterized by the lack of both the A and B subunits; and type II deficiency, characterized by the lack of the A subunit alone. These defects can result in a lifelong bleeding tendency, defective wound healing, and habitual abortion. [provided by RefSeq, Jul 2008]

F13B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

PM1

In a disulfide_bond (size 44) in uniprot entity F13B_HUMAN there are 5 pathogenic changes around while only 0 benign (100%) in NM_001994.3

BP4

Computational evidence support a benign effect (MetaRNN=6.8317645E-6).

BP6

Variant 1-197061891-C-T is Benign according to our data. Variant chr1-197061891-C-T is described in ClinVar as [Benign]. Clinvar id is 16520.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-197061891-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.956 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
F13B	NM_001994.3 linkuse as main transcript	c.344G>A	p.Arg115His	missense_variant	3/12	ENST00000367412.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
F13B	ENST00000367412.2 linkuse as main transcript	c.344G>A	p.Arg115His	missense_variant	3/12	1	NM_001994.3	P1

Frequencies

GnomAD3 genomes

AF:

0.770

AC:

116834

AN:

151792

Hom.:

48890

Cov.:

show subpopulations

Gnomad AFR

AF:

0.403

Gnomad AMI

AF:

0.955

Gnomad AMR

AF:

0.868

Gnomad ASJ

AF:

0.902

Gnomad EAS

AF:

0.979

Gnomad SAS

AF:

0.896

Gnomad FIN

AF:

0.929

Gnomad MID

AF:

0.886

Gnomad NFE

AF:

0.910

Gnomad OTH

AF:

0.800

GnomAD3 exomes

AF:

0.882

AC:

220834

AN:

250328

Hom.:

99690

AF XY:

0.890

AC XY:

120395

AN XY:

135260

show subpopulations

Gnomad AFR exome

AF:

0.391

Gnomad AMR exome

AF:

0.932

Gnomad ASJ exome

AF:

0.894

Gnomad EAS exome

AF:

0.982

Gnomad SAS exome

AF:

0.898

Gnomad FIN exome

AF:

0.930

Gnomad NFE exome

AF:

0.906

Gnomad OTH exome

AF:

0.897

GnomAD4 exome

AF:

0.894

AC:

1306317

AN:

1460740

Hom.:

589189

Cov.:

AF XY:

0.896

AC XY:

651004

AN XY:

726666

show subpopulations

Gnomad4 AFR exome

AF:

0.382

Gnomad4 AMR exome

AF:

0.927

Gnomad4 ASJ exome

AF:

0.900

Gnomad4 EAS exome

AF:

0.982

Gnomad4 SAS exome

AF:

0.898

Gnomad4 FIN exome

AF:

0.932

Gnomad4 NFE exome

AF:

0.904

Gnomad4 OTH exome

AF:

0.879

GnomAD4 genome

AF:

0.770

AC:

116902

AN:

151910

Hom.:

48909

Cov.:

AF XY:

0.775

AC XY:

57553

AN XY:

74276

show subpopulations

Gnomad4 AFR

AF:

0.403

Gnomad4 AMR

AF:

0.868

Gnomad4 ASJ

AF:

0.902

Gnomad4 EAS

AF:

0.979

Gnomad4 SAS

AF:

0.897

Gnomad4 FIN

AF:

0.929

Gnomad4 NFE

AF:

0.910

Gnomad4 OTH

AF:

0.802

Alfa

AF:

0.889

Hom.:

156847

Bravo

AF:

0.749

ESP6500AA

AF:

0.409

AC:

1804

ESP6500EA

AF:

0.907

AC:

7801

ExAC

AF:

0.872

AC:

105765

Asia WGS

AF:

0.911

AC:

3166

AN:

3476

EpiCase

AF:

0.905

EpiControl

AF:

0.909

ClinVar

Significance: Benign

Submissions summary: Benign:6Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Factor XIII, b subunit, deficiency of

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Aug 10, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Mar 06, 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. -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 10, 2018

This variant is associated with the following publications: (PMID: 27821352, 12941053, 25384012, 16241947, 12456499) -

Venous thrombosis, susceptibility to

Other:1

risk factor, no assertion criteria provided

literature only

OMIM

Nov 01, 2005

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.057

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.57

CADD

Benign

0.64

DANN

Benign

0.31

DEOGEN2

Benign

0.16

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.016

LIST_S2

Benign

0.53

MetaRNN

Benign

0.0000068

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.79

MutationTaster

Benign

1.0

PrimateAI

Benign

0.25

PROVEAN

Benign

-0.51

REVEL

Benign

0.037

Sift

Benign

0.38

Sift4G

Benign

0.74

Polyphen

0.0

Vest4

0.018

MPC

0.16

ClinPred

0.0072

GERP RS

-0.82

Varity_R

0.032

gMVP

0.59

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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