6-82194488-C-T
Position:
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_015525.4(IBTK):c.3329G>A(p.Gly1110Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Consequence
IBTK
NM_015525.4 missense
NM_015525.4 missense
Scores
18
Clinical Significance
Conservation
PhyloP100: 0.724
Genes affected
IBTK (HGNC:17853): (inhibitor of Bruton tyrosine kinase) Bruton tyrosine kinase (BTK) is a protein tyrosine kinase that is expressed in B cells, macrophages, and neutrophils. The protein encoded by this gene binds to BTK and downregulates BTK's kinase activity. In addition, the encoded protein disrupts BTK-mediated calcium mobilization and negatively regulates the activation of nuclear factor-kappa-B-driven transcription. This gene has a pseudogene on chromosome 18. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Jul 2014]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.058138847).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
IBTK | NM_015525.4 | c.3329G>A | p.Gly1110Asp | missense_variant | 23/29 | ENST00000306270.12 | |
IBTK | NM_001300906.2 | c.3284G>A | p.Gly1095Asp | missense_variant | 23/29 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
IBTK | ENST00000306270.12 | c.3329G>A | p.Gly1110Asp | missense_variant | 23/29 | 1 | NM_015525.4 | P1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD3 exomes AF: 0.00000440 AC: 1AN: 227376Hom.: 0 AF XY: 0.00000814 AC XY: 1AN XY: 122904
GnomAD3 exomes
AF:
AC:
1
AN:
227376
Hom.:
AF XY:
AC XY:
1
AN XY:
122904
Gnomad AFR exome
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GnomAD4 exome Cov.: 30
GnomAD4 exome
Cov.:
30
GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
ExAC
AF:
AC:
1
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 06, 2021 | The c.3329G>A (p.G1110D) alteration is located in exon 23 (coding exon 22) of the IBTK gene. This alteration results from a G to A substitution at nucleotide position 3329, causing the glycine (G) at amino acid position 1110 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
DEOGEN2
Benign
T;.;.;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;.;.;.
MutationTaster
Benign
N;N;N
PrimateAI
Benign
T
PROVEAN
Benign
N;.;N;N
REVEL
Benign
Sift
Benign
T;.;T;T
Sift4G
Benign
T;T;T;T
Polyphen
B;B;B;B
Vest4
MutPred
Gain of disorder (P = 0.171);.;.;.;
MVP
MPC
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at