rs6000

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001994.3(F13B):c.1707T>G(p.Asp569Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00337 in 1,613,206 control chromosomes in the GnomAD database, including 109 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.015 ( 53 hom., cov: 32)

Exomes 𝑓: 0.0021 ( 56 hom. )

Consequence

F13B
NM_001994.3 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -6.02

Publications

17 publications found

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 Gene-Disease associations (from GenCC):

factor XIII, b subunit, deficiency of
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics
congenital factor XIII deficiency
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

F13B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005678028).

BP6

Variant 1-197050728-A-C is Benign according to our data. Variant chr1-197050728-A-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 294572.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0151 (2303/152200) while in subpopulation AFR AF = 0.0491 (2041/41548). AF 95% confidence interval is 0.0473. There are 53 homozygotes in GnomAd4. There are 1110 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 53 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
F13B	NM_001994.3 link	c.1707T>G	p.Asp569Glu	missense_variant	Exon 10 of 12	ENST00000367412.2	NP_001985.2	P05160

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
F13B	ENST00000367412.2 link	c.1707T>G	p.Asp569Glu	missense_variant	Exon 10 of 12	1	NM_001994.3	ENSP00000356382.2	P05160
F13B	ENST00000649282.1 link	c.462T>G	p.Asp154Glu	missense_variant	Exon 3 of 5			ENSP00000497116.1	A0A3B3IS66
F13B	ENST00000490002.1 link	n.118T>G		non_coding_transcript_exon_variant	Exon 1 of 3	3

Frequencies

GnomAD3 genomes

AF:

0.0151

AC:

2298

AN:

152082

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0491

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00683

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0202

Gnomad SAS

AF:

0.00207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000324

Gnomad OTH

AF:

0.00911

GnomAD2 exomes

AF:

0.00528

AC:

1325

AN:

250800

AF XY:

0.00409

show subpopulations

Gnomad AFR exome

AF:

0.0496

Gnomad AMR exome

AF:

0.00320

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0178

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000317

Gnomad OTH exome

AF:

0.00344

GnomAD4 exome

AF:

0.00215

AC:

3138

AN:

1461006

Hom.:

Cov.:

AF XY:

0.00198

AC XY:

1437

AN XY:

726828

show subpopulations

African (AFR)

AF:

0.0495

AC:

1653

AN:

33408

American (AMR)

AF:

0.00323

AC:

144

AN:

44590

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26098

East Asian (EAS)

AF:

0.0176

AC:

697

AN:

39644

South Asian (SAS)

AF:

0.000904

AC:

AN:

86252

European-Finnish (FIN)

AF:

0.0000375

AC:

AN:

53368

Middle Eastern (MID)

AF:

0.00312

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.000222

AC:

247

AN:

1111544

Other (OTH)

AF:

0.00496

AC:

299

AN:

60340

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

149

298

446

595

744

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

136

204

272

340

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0151

AC:

2303

AN:

152200

Hom.:

Cov.:

AF XY:

0.0149

AC XY:

1110

AN XY:

74414

show subpopulations

African (AFR)

AF:

0.0491

AC:

2041

AN:

41548

American (AMR)

AF:

0.00682

AC:

104

AN:

15254

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3464

East Asian (EAS)

AF:

0.0200

AC:

104

AN:

5188

South Asian (SAS)

AF:

0.00207

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000324

AC:

AN:

67990

Other (OTH)

AF:

0.00901

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

110

220

330

440

550

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

104

130

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00554

Hom.:

Bravo

AF:

0.0162

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.0481

AC:

212

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00602

AC:

731

Asia WGS

AF:

0.00866

AC:

AN:

3478

EpiCase

AF:

0.000327

EpiControl

AF:

0.000415

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Factor XIII, b subunit, deficiency of

Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Likely 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.66

CADD

Benign

0.013

(source)

DANN

Benign

0.27

DEOGEN2

Benign

0.17

.;T

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.0054

LIST_S2

Benign

0.062

T;T

MetaRNN

Benign

0.0057

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.71

.;N

PhyloP100

-6.0

PrimateAI

Benign

0.27

PROVEAN

Benign

-0.25

.;N

REVEL

Benign

0.067

Sift

Benign

1.0

.;T

Sift4G

Benign

1.0

.;T

Polyphen

0.0010

.;B

Vest4

0.10

MutPred

0.44

.;Gain of phosphorylation at Y566 (P = 0.09);

MVP

0.42

MPC

0.12

ClinPred

0.97

GERP RS

-9.0

Varity_R

0.037

gMVP

0.26

Mutation Taster

=97/3

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over