1-197040740-GAAC-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP6BS1BS2

The NM_001994.3(F13B):c.1739-8_1739-6delGTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00186 in 1,593,662 control chromosomes in the GnomAD database, including 5 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0018 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0019 ( 5 hom. )

Consequence

F13B
NM_001994.3 splice_region, intron

Scores

Not classified

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:2

Conservation

PhyloP100: 0.946

Publications

0 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 -9 ACMG points.

BP6

Variant 1-197040740-GAAC-G is Benign according to our data. Variant chr1-197040740-GAAC-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 294571.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Likely_benign=2}.

BS1

Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.00184 (280/151848) while in subpopulation AMR AF = 0.00664 (101/15222). AF 95% confidence interval is 0.00559. There are 0 homozygotes in GnomAd4. There are 154 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAdExome4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
F13B	NM_001994.3 link	c.1739-8_1739-6delGTT		splice_region_variant, intron_variant	Intron 10 of 11	ENST00000367412.2	NP_001985.2	P05160

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
F13B	ENST00000367412.2 link	c.1739-8_1739-6delGTT	splice_region_variant, intron_variant	Intron 10 of 11	1	NM_001994.3	ENSP00000356382.2	P05160
F13B	ENST00000649282.1 link	c.494-8_494-6delGTT	splice_region_variant, intron_variant	Intron 3 of 4			ENSP00000497116.1	A0A3B3IS66
F13B	ENST00000490002.1 link	n.150-8_150-6delGTT	splice_region_variant, intron_variant	Intron 1 of 2	3

Frequencies

GnomAD3 genomes

AF:

0.00185

AC:

280

AN:

151730

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000630

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00664

Gnomad ASJ

AF:

0.000289

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00208

Gnomad OTH

AF:

0.00527

GnomAD2 exomes

AF:

0.00163

AC:

385

AN:

236506

AF XY:

0.00155

show subpopulations

Gnomad AFR exome

AF:

0.000522

Gnomad AMR exome

AF:

0.00470

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000471

Gnomad NFE exome

AF:

0.00196

Gnomad OTH exome

AF:

0.00241

GnomAD4 exome

AF:

0.00187

AC:

2692

AN:

1441814

Hom.:

AF XY:

0.00181

AC XY:

1296

AN XY:

717694

show subpopulations

African (AFR)

AF:

0.000396

AC:

AN:

32812

American (AMR)

AF:

0.00434

AC:

189

AN:

43510

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25874

East Asian (EAS)

AF:

0.00

AC:

AN:

39372

South Asian (SAS)

AF:

0.00

AC:

AN:

84164

European-Finnish (FIN)

AF:

0.0000942

AC:

AN:

53096

Middle Eastern (MID)

AF:

0.000177

AC:

AN:

5634

European-Non Finnish (NFE)

AF:

0.00219

AC:

2404

AN:

1097784

Other (OTH)

AF:

0.00134

AC:

AN:

59568

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

124

248

372

496

620

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00184

AC:

280

AN:

151848

Hom.:

Cov.:

AF XY:

0.00207

AC XY:

154

AN XY:

74220

show subpopulations

African (AFR)

AF:

0.000628

AC:

AN:

41416

American (AMR)

AF:

0.00664

AC:

101

AN:

15222

Ashkenazi Jewish (ASJ)

AF:

0.000289

AC:

AN:

3464

East Asian (EAS)

AF:

0.00

AC:

AN:

5164

South Asian (SAS)

AF:

0.00

AC:

AN:

4814

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10536

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00208

AC:

141

AN:

67916

Other (OTH)

AF:

0.00521

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00142

Hom.:

Bravo

AF:

0.00219

Asia WGS

AF:

0.000289

AC:

AN:

3474

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:2

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Benign:2

Mar 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

F13B: BP4 -

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Factor XIII, b subunit, deficiency of

Uncertain:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.95

Mutation Taster

=95/5

polymorphism

(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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1-197040740-GAAC-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