Variant 20-37732936-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_030877.5(CTNNBL1):c.88C>T(p.Arg30Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000684 in 1,461,712 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: not found (cov: 32)

Exomes 𝑓: 0.0000068 ( 0 hom. )

Consequence

CTNNBL1
NM_030877.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.64

Variant links:

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]

CTNNBL1 links:

CTNNBL1 (HGNC:):

CTNNBL1 links:

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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=0.26534265).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CTNNBL1	NM_030877.5 linkuse as main transcript	c.88C>T	p.Arg30Trp	missense_variant	2/16	ENST00000361383.11	NP_110517.2	Q8WYA6-1
CTNNBL1	NM_001281495.2 linkuse as main transcript	c.7C>T	p.Arg3Trp	missense_variant	3/17		NP_001268424.1	Q8WYA6-4
CTNNBL1	XM_024451947.2 linkuse as main transcript	c.7C>T	p.Arg3Trp	missense_variant	3/17		XP_024307715.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CTNNBL1	ENST00000361383.11 linkuse as main transcript	c.88C>T	p.Arg30Trp	missense_variant	2/16	1	NM_030877.5	ENSP00000355050.6	Q8WYA6-1
CTNNBL1	ENST00000628103.2 linkuse as main transcript	c.7C>T	p.Arg3Trp	missense_variant	3/17	2		ENSP00000487198.1	Q8WYA6-4
CTNNBL1	ENST00000447935.3 linkuse as main transcript	c.7C>T	p.Arg3Trp	missense_variant	3/7	5		ENSP00000394464.1	A2A2P1
CTNNBL1	ENST00000621317.4 linkuse as main transcript	c.88C>T	p.Arg30Trp	missense_variant	2/17	5			A0A087WUB9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000684

AC:

AN:

1461712

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

727164

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000719

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000355

Hom.:

Bravo

AF:

0.0000113

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

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

Jun 22, 2024

The c.88C>T (p.R30W) alteration is located in exon 2 (coding exon 2) of the CTNNBL1 gene. This alteration results from a C to T substitution at nucleotide position 88, causing the arginine (R) at amino acid position 30 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.059

BayesDel_noAF

Benign

-0.32

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.24

.;.;T;.;.

Eigen

Uncertain

0.45

Eigen_PC

Uncertain

0.46

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.81

T;T;T;T;.

M_CAP

Benign

0.016

MetaRNN

Benign

0.27

T;T;T;T;T

MetaSVM

Benign

-0.82

MutationAssessor

Benign

1.9

.;.;L;.;.

PrimateAI

Uncertain

0.57

PROVEAN

Uncertain

-2.8

.;D;N;D;.

REVEL

Benign

0.11

Sift

Uncertain

0.0010

.;D;D;D;.

Sift4G

Uncertain

0.0050

D;D;D;D;D

Polyphen

0.99, 1.0

.;.;D;D;.

Vest4

0.58

MutPred

0.21

Loss of solvent accessibility (P = 0.0509);.;Loss of solvent accessibility (P = 0.0509);.;.;

MVP

0.53

MPC

0.78

ClinPred

0.97

GERP RS

4.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.18

gMVP

0.45

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over