chrX-101375133-G-A
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2
The NM_000061.3(BTK):c.141+11C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00773 in 1,209,389 control chromosomes in the GnomAD database, including 29 homozygotes. There are 2,872 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_000061.3 intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
BTK | NM_000061.3 | c.141+11C>T | intron_variant | Intron 2 of 18 | ENST00000308731.8 | NP_000052.1 | ||
BTK | NM_001287344.2 | c.243+11C>T | intron_variant | Intron 2 of 18 | NP_001274273.1 | |||
BTK | NM_001287345.2 | c.141+11C>T | intron_variant | Intron 3 of 16 | NP_001274274.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00605 AC: 677AN: 111813Hom.: 1 Cov.: 23 AF XY: 0.00515 AC XY: 175AN XY: 33993
GnomAD3 exomes AF: 0.00482 AC: 882AN: 183166Hom.: 1 AF XY: 0.00477 AC XY: 323AN XY: 67704
GnomAD4 exome AF: 0.00790 AC: 8667AN: 1097523Hom.: 28 Cov.: 30 AF XY: 0.00743 AC XY: 2697AN XY: 362901
GnomAD4 genome AF: 0.00605 AC: 677AN: 111866Hom.: 1 Cov.: 23 AF XY: 0.00514 AC XY: 175AN XY: 34056
ClinVar
Submissions by phenotype
not provided Benign:4
BTK: BP4, BS1, BS2 -
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Variant summary: The BTK c.141+11C>T variant involves the alteration of a non-conserved intronic nucleotide. Mutation tested predicts a benign outcome for this variant. 5/5 splice prediction tools predict no significant impact on normal splicing. These predictions have yet to be confirmed by functional studies. This variant was found in the large control population database ExAC (410/87888 control chromosomes including 160 hemizygotes) at a frequency of 0.004665, which is approximately 2 times the estimated maximal expected allele frequency of a pathogenic BTK variant (0.0023049), suggesting this variant is likely a benign polymorphism. Multiple clinical diagnostic laboratories/reputable databases have classified this variant as likely benign or benign. Published studies als support for benign outcome -- this variant was found not to cosegregate with XLA in a family (Conley_2008) and was found in a family with primary immunodeficiency disease that had alternate molecular mechanism (Stray-Pedersen_2017). Taken together, this variant is classified as benign. -
not specified Benign:2
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This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
X-linked agammaglobulinemia with growth hormone deficiency Benign:2
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This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -
X-linked agammaglobulinemia Benign:2
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This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -
X-linked agammaglobulinemia;C0472813:X-linked agammaglobulinemia with growth hormone deficiency Uncertain:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at