chr20-37860333-A-G
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_030877.5(CTNNBL1):c.1592A>G(p.His531Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000134 in 1,613,574 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000072 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00014 ( 0 hom. )
Consequence
CTNNBL1
NM_030877.5 missense
NM_030877.5 missense
Scores
2
3
9
Clinical Significance
Conservation
PhyloP100: 8.86
Genes affected
CTNNBL1 (HGNC:15879): (catenin beta like 1) The protein encoded by this gene is a component of the pre-mRNA-processing factor 19-cell division cycle 5-like (PRP19-CDC5L) protein complex, which activates pre-mRNA splicing and is an integral part of the spliceosome. The encoded protein is also a nuclear localization sequence binding protein, and binds to activation-induced deaminase and is important for antibody diversification. This gene may also be associated with the development of obesity. Alternative splicing results in multiple transcript variants. A pseudogene of this gene has been defined on the X chromosome. [provided by RefSeq, Jul 2013]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.3299637).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CTNNBL1 | NM_030877.5 | c.1592A>G | p.His531Arg | missense_variant | 15/16 | ENST00000361383.11 | |
CTNNBL1 | NM_001281495.2 | c.1511A>G | p.His504Arg | missense_variant | 16/17 | ||
CTNNBL1 | XM_024451947.2 | c.1511A>G | p.His504Arg | missense_variant | 16/17 | ||
CTNNBL1 | XM_011528917.3 | c.1262A>G | p.His421Arg | missense_variant | 13/14 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CTNNBL1 | ENST00000361383.11 | c.1592A>G | p.His531Arg | missense_variant | 15/16 | 1 | NM_030877.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000723 AC: 11AN: 152230Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000875 AC: 22AN: 251474Hom.: 0 AF XY: 0.0000809 AC XY: 11AN XY: 135904
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GnomAD4 exome AF: 0.000140 AC: 205AN: 1461344Hom.: 0 Cov.: 30 AF XY: 0.000125 AC XY: 91AN XY: 727048
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GnomAD4 genome ? AF: 0.0000723 AC: 11AN: 152230Hom.: 0 Cov.: 33 AF XY: 0.0000538 AC XY: 4AN XY: 74378
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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 | Sep 14, 2021 | The c.1592A>G (p.H531R) alteration is located in exon 15 (coding exon 15) of the CTNNBL1 gene. This alteration results from a A to G substitution at nucleotide position 1592, causing the histidine (H) at amino acid position 531 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Benign
Eigen
Benign
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D;.;D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D
PrimateAI
Pathogenic
D
Sift4G
Benign
T;T;T;T;T;T
Polyphen
0.11, 0.14
.;.;B;.;B;.
Vest4
MVP
MPC
0.62
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
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