chr1-197050892-G-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_001994.3(F13B):c.1556-13C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00145 in 1,607,192 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0011 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0015 ( 16 hom. )

Consequence

F13B
NM_001994.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.315

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: Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen
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 -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.76).

BP6

Variant 1-197050892-G-T is Benign according to our data. Variant chr1-197050892-G-T is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 258503.

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00108 (164/152270) while in subpopulation SAS AF = 0.0122 (59/4828). AF 95% confidence interval is 0.00973. There are 3 homozygotes in GnomAd4. There are 99 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001994.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	F13B	NM_001994.3	MANE Select	c.1556-13C>A		intron	N/A	NP_001985.2	P05160

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
F13B	ENST00000367412.2	TSL:1 MANE Select	c.1556-13C>A	intron	N/A	ENSP00000356382.2	P05160
F13B	ENST00000895404.1		c.1373-13C>A	intron	N/A	ENSP00000565463.1
F13B	ENST00000895399.1		c.1355-13C>A	intron	N/A	ENSP00000565458.1

Frequencies

GnomAD3 genomes

AF:

0.00107

AC:

163

AN:

152152

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0120

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00104

Gnomad OTH

AF:

0.00143

GnomAD2 exomes

AF:

0.00231

AC:

574

AN:

248876

AF XY:

0.00289

show subpopulations

Gnomad AFR exome

AF:

0.0000621

Gnomad AMR exome

AF:

0.000350

Gnomad ASJ exome

AF:

0.00789

Gnomad EAS exome

AF:

0.0000546

Gnomad FIN exome

AF:

0.0000936

Gnomad NFE exome

AF:

0.00114

Gnomad OTH exome

AF:

0.00231

GnomAD4 exome

AF:

0.00149

AC:

2162

AN:

1454922

Hom.:

Cov.:

AF XY:

0.00182

AC XY:

1320

AN XY:

724160

show subpopulations

African (AFR)

AF:

0.000120

AC:

AN:

33304

American (AMR)

AF:

0.000337

AC:

AN:

44550

Ashkenazi Jewish (ASJ)

AF:

0.00841

AC:

219

AN:

26044

East Asian (EAS)

AF:

0.00

AC:

AN:

39574

South Asian (SAS)

AF:

0.0108

AC:

927

AN:

86046

European-Finnish (FIN)

AF:

0.000113

AC:

AN:

53006

Middle Eastern (MID)

AF:

0.00785

AC:

AN:

5732

European-Non Finnish (NFE)

AF:

0.000741

AC:

820

AN:

1106596

Other (OTH)

AF:

0.00210

AC:

126

AN:

60070

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

104

208

312

416

520

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

126

168

210

<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:

0.00108

AC:

164

AN:

152270

Hom.:

Cov.:

AF XY:

0.00133

AC XY:

AN XY:

74444

show subpopulations

African (AFR)

AF:

0.0000962

AC:

AN:

41564

American (AMR)

AF:

0.000262

AC:

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.00576

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.0122

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00104

AC:

AN:

68020

Other (OTH)

AF:

0.00142

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00114

Hom.:

Bravo

AF:

0.000744

Asia WGS

AF:

0.00202

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

Factor XIII, b subunit, deficiency of (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

8.5

(source)

DANN

Benign

0.67

PhyloP100

-0.32

Mutation Taster

=100/0

polymorphism

(source)

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

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over