Variant 1-9871229-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_020248.3(CTNNBIP1):c.145A>G(p.Asn49Asp) variant causes a missense change. The variant allele was found at a frequency of 0.000000699 in 1,429,614 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/19 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)

Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

CTNNBIP1
NM_020248.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.12

Variant links:

Genes affected

CTNNBIP1 (HGNC:16913): (catenin beta interacting protein 1) The protein encoded by this gene binds CTNNB1 and prevents interaction between CTNNB1 and TCF family members. The encoded protein is a negative regulator of the Wnt signaling pathway. Two transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jul 2008]

CTNNBIP1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2509811).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CTNNBIP1	NM_020248.3 linkuse as main transcript	c.145A>G	p.Asn49Asp	missense_variant	5/6	ENST00000377263.6	NP_064633.1	Q9NSA3A0A024R4D7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CTNNBIP1	ENST00000377263.6 linkuse as main transcript	c.145A>G	p.Asn49Asp	missense_variant	5/6	1	NM_020248.3	ENSP00000366474.1	Q9NSA3
CTNNBIP1	ENST00000400904.7 linkuse as main transcript	c.145A>G	p.Asn49Asp	missense_variant	4/5	1		ENSP00000383696.3	Q9NSA3
CTNNBIP1	ENST00000377256.1 linkuse as main transcript	c.145A>G	p.Asn49Asp	missense_variant	4/5	5		ENSP00000366466.1	Q9NSA3
CTNNBIP1	ENST00000377258.5 linkuse as main transcript	c.145A>G	p.Asn49Asp	missense_variant	4/5	3		ENSP00000366468.1	Q9NSA3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.99e-7

AC:

AN:

1429614

Hom.:

Cov.:

AF XY:

0.00000141

AC XY:

AN XY:

707706

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:

9.12e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000838

AC:

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

May 26, 2022

The c.145A>G (p.N49D) alteration is located in exon 5 (coding exon 2) of the CTNNBIP1 gene. This alteration results from a A to G substitution at nucleotide position 145, causing the asparagine (N) at amino acid position 49 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: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.60

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Uncertain

0.45

T;T;T;T

Eigen

Benign

-0.23

Eigen_PC

Benign

-0.099

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.83

.;.;.;T

M_CAP

Benign

0.0051

MetaRNN

Benign

0.25

T;T;T;T

MetaSVM

Benign

-0.96

PrimateAI

Benign

0.34

PROVEAN

Uncertain

-2.4

N;N;N;N

REVEL

Benign

0.084

Sift

Benign

0.16

T;T;T;T

Sift4G

Benign

0.18

T;T;T;T

Polyphen

0.0020

B;B;B;B

Vest4

0.24

MutPred

0.55

Gain of loop (P = 0.0851);Gain of loop (P = 0.0851);Gain of loop (P = 0.0851);Gain of loop (P = 0.0851);

MVP

0.28

MPC

0.37

ClinPred

0.87

GERP RS

3.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.23

gMVP

0.55

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