rs3024480
Positions:
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2
The NM_000129.4(F13A1):c.1112+17A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00827 in 1,612,940 control chromosomes in the GnomAD database, including 114 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.013 ( 33 hom., cov: 32)
Exomes 𝑓: 0.0077 ( 81 hom. )
Consequence
F13A1
NM_000129.4 intron
NM_000129.4 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.549
Genes affected
F13A1 (HGNC:3531): (coagulation factor XIII A chain) This gene encodes the coagulation factor XIII A 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 plasma carrier molecules. Platelet factor XIII is comprised only of 2 A subunits, which are identical to those of plasma origin. Upon 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. It also crosslinks alpha-2-plasmin inhibitor, or fibronectin, to the alpha chains of fibrin. 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 -14 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BP6
?
Variant 6-6222016-T-C is Benign according to our data. Variant chr6-6222016-T-C is described in ClinVar as [Benign]. Clinvar id is 255182.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0133 (2023/152308) while in subpopulation AFR AF= 0.0262 (1089/41558). AF 95% confidence interval is 0.0249. There are 33 homozygotes in gnomad4. There are 966 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 33 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
F13A1 | NM_000129.4 | c.1112+17A>G | intron_variant | ENST00000264870.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
F13A1 | ENST00000264870.8 | c.1112+17A>G | intron_variant | 1 | NM_000129.4 | P1 | |||
F13A1 | ENST00000445223.1 | c.262+17A>G | intron_variant | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0132 AC: 2009AN: 152190Hom.: 33 Cov.: 32
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GnomAD3 exomes AF: 0.00892 AC: 2233AN: 250316Hom.: 23 AF XY: 0.00901 AC XY: 1219AN XY: 135334
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GnomAD4 exome AF: 0.00774 AC: 11308AN: 1460632Hom.: 81 Cov.: 31 AF XY: 0.00790 AC XY: 5744AN XY: 726684
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GnomAD4 genome ? AF: 0.0133 AC: 2023AN: 152308Hom.: 33 Cov.: 32 AF XY: 0.0130 AC XY: 966AN XY: 74484
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at