1-197040668-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001994.3(F13B):c.1806T>C(p.Asn602Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.488 in 1,611,534 control chromosomes in the GnomAD database, including 200,693 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.44 ( 16615 hom., cov: 32)

Exomes 𝑓: 0.49 ( 184078 hom. )

Consequence

F13B
NM_001994.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -0.430

Publications

21 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.53).

BP6

Variant 1-197040668-A-G is Benign according to our data. Variant chr1-197040668-A-G is described in ClinVar as [Benign]. Clinvar id is 258504.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.43 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.801 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
F13B	NM_001994.3 link	c.1806T>C	p.Asn602Asn	synonymous_variant	Exon 11 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.1806T>C	p.Asn602Asn	synonymous_variant	Exon 11 of 12	1	NM_001994.3	ENSP00000356382.2	P05160
F13B	ENST00000649282.1 link	c.561T>C	p.Asn187Asn	synonymous_variant	Exon 4 of 5			ENSP00000497116.1	A0A3B3IS66
F13B	ENST00000490002.1 link	n.217T>C		non_coding_transcript_exon_variant	Exon 2 of 3	3

Frequencies

GnomAD3 genomes

AF:

0.442

AC:

67131

AN:

151716

Hom.:

16603

Cov.:

show subpopulations

Gnomad AFR

AF:

0.234

Gnomad AMI

AF:

0.557

Gnomad AMR

AF:

0.591

Gnomad ASJ

AF:

0.488

Gnomad EAS

AF:

0.822

Gnomad SAS

AF:

0.604

Gnomad FIN

AF:

0.556

Gnomad MID

AF:

0.427

Gnomad NFE

AF:

0.473

Gnomad OTH

AF:

0.458

GnomAD2 exomes

AF:

0.540

AC:

135126

AN:

250204

AF XY:

0.538

show subpopulations

Gnomad AFR exome

AF:

0.228

Gnomad AMR exome

AF:

0.721

Gnomad ASJ exome

AF:

0.488

Gnomad EAS exome

AF:

0.818

Gnomad FIN exome

AF:

0.566

Gnomad NFE exome

AF:

0.472

Gnomad OTH exome

AF:

0.524

GnomAD4 exome

AF:

0.493

AC:

719945

AN:

1459698

Hom.:

184078

Cov.:

AF XY:

0.496

AC XY:

360210

AN XY:

726220

show subpopulations

African (AFR)

AF:

0.226

AC:

7566

AN:

33414

American (AMR)

AF:

0.707

AC:

31565

AN:

44634

Ashkenazi Jewish (ASJ)

AF:

0.492

AC:

12828

AN:

26098

East Asian (EAS)

AF:

0.828

AC:

32788

AN:

39588

South Asian (SAS)

AF:

0.588

AC:

50697

AN:

86190

European-Finnish (FIN)

AF:

0.562

AC:

30019

AN:

53372

Middle Eastern (MID)

AF:

0.480

AC:

2758

AN:

5740

European-Non Finnish (NFE)

AF:

0.470

AC:

521634

AN:

1110350

Other (OTH)

AF:

0.499

AC:

30090

AN:

60312

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

16778

33556

50334

67112

83890

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.442

AC:

67163

AN:

151836

Hom.:

16615

Cov.:

AF XY:

0.453

AC XY:

33582

AN XY:

74210

show subpopulations

African (AFR)

AF:

0.234

AC:

9703

AN:

41434

American (AMR)

AF:

0.592

AC:

9021

AN:

15238

Ashkenazi Jewish (ASJ)

AF:

0.488

AC:

1691

AN:

3464

East Asian (EAS)

AF:

0.822

AC:

4236

AN:

5156

South Asian (SAS)

AF:

0.603

AC:

2904

AN:

4816

European-Finnish (FIN)

AF:

0.556

AC:

5872

AN:

10552

Middle Eastern (MID)

AF:

0.429

AC:

126

AN:

294

European-Non Finnish (NFE)

AF:

0.473

AC:

32129

AN:

67862

Other (OTH)

AF:

0.462

AC:

974

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1775

3550

5326

7101

8876

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.464

Hom.:

48148

Bravo

AF:

0.439

Asia WGS

AF:

0.700

AC:

2424

AN:

3466

EpiCase

AF:

0.481

EpiControl

AF:

0.482

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Nov 12, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Factor XIII, b subunit, deficiency of

Benign:2

Jan 13, 2018

Illumina Laboratory Services, Illumina

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

Aug 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

0.97

(source)

DANN

Benign

0.54

PhyloP100

-0.43

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

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1-197040668-A-G

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