1-9871231-A-C

Position:

• chr1-9871231-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_020248.3(CTNNBIP1):​c.143T>G​(p.Val48Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CTNNBIP1 NM_020248.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.01

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CTNNBIP1	NM_020248.3	c.143T>G	p.Val48Gly	missense_variant	5/6	ENST00000377263.6	NP_064633.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CTNNBIP1	ENST00000377263.6	c.143T>G	p.Val48Gly	missense_variant	5/6	1	NM_020248.3	ENSP00000366474.1
CTNNBIP1	ENST00000400904.7	c.143T>G	p.Val48Gly	missense_variant	4/5	1		ENSP00000383696.3
CTNNBIP1	ENST00000377256.1	c.143T>G	p.Val48Gly	missense_variant	4/5	5		ENSP00000366466.1
CTNNBIP1	ENST00000377258.5	c.143T>G	p.Val48Gly	missense_variant	4/5	3		ENSP00000366468.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 19, 2024

The c.143T>G (p.V48G) alteration is located in exon 5 (coding exon 2) of the CTNNBIP1 gene. This alteration results from a T to G substitution at nucleotide position 143, causing the valine (V) at amino acid position 48 to be replaced by a glycine (G). 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	Pathogenic	0.59
BayesDel_addAF	Pathogenic	0.24	D
BayesDel_noAF	Uncertain	0.10
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.51	D;D;D;D
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.14
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.72	.;.;.;T
M_CAP	Benign	0.061	D
MetaRNN	Uncertain	0.63	D;D;D;D
MetaSVM	Benign	-1.1	T
PrimateAI	Uncertain	0.53	T
PROVEAN	Pathogenic	-5.2	D;D;D;D
REVEL	Benign	0.22
Sift	Uncertain	0.0010	D;D;D;D
Sift4G	Pathogenic	0.0	D;D;D;D
Polyphen		0.15	B;B;B;B
Vest4		0.62
MutPred		0.66		Gain of relative solvent accessibility (P = 0.005);Gain of relative solvent accessibility (P = 0.005);Gain of relative solvent accessibility (P = 0.005);Gain of relative solvent accessibility (P = 0.005);
MVP		0.50
MPC		0.49
ClinPred		0.99	D
GERP RS		2.6
Varity_R		0.86
gMVP		0.67

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-9931289;