1-197040740-GAAC-G
Variant summary
Our verdict is Benign. Variant got -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
NM_001994.3 splice_region, intron
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.946
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -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: {Likely_benign=2, Uncertain_significance=1}.
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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAdExome4 at 5 AR gene
Transcripts
RefSeq
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| F13B | ENST00000367412.2 | c.1739-8_1739-6delGTT | splice_region_variant, intron_variant | Intron 10 of 11 | 1 | NM_001994.3 | ENSP00000356382.2 | |||
| F13B | ENST00000649282.1 | c.494-8_494-6delGTT | splice_region_variant, intron_variant | Intron 3 of 4 | ENSP00000497116.1 | |||||
| F13B | ENST00000490002.1 | n.150-8_150-6delGTT | splice_region_variant, intron_variant | Intron 1 of 2 | 3 |
Frequencies
GnomAD3 genomes 0.00185 AC: 280AN: 151730Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00163 AC: 385AN: 236506Hom.: 2 AF XY: 0.00155 AC XY: 198AN XY: 127878
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GnomAD4 exome AF: 0.00187 AC: 2692AN: 1441814Hom.: 5 AF XY: 0.00181 AC XY: 1296AN XY: 717694
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GnomAD4 genome 0.00184 AC: 280AN: 151848Hom.: 0 Cov.: 32 AF XY: 0.00207 AC XY: 154AN XY: 74220
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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
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at