22-24050841-G-A

Position:

chr22-24050841-G-A

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 1P and 20B. PP2BP4_StrongBP6_Very_StrongBA1

The NM_012295.4(CABIN1):c.673G>A(p.Asp225Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0221 in 1,614,074 control chromosomes in the GnomAD database, including 713 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.041 ( 243 hom., cov: 32)

Exomes 𝑓: 0.020 ( 470 hom. )

Consequence

CABIN1
NM_012295.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 2.51

Variant links:

Genes affected

CABIN1 (HGNC:24187): (calcineurin binding protein 1) Calcineurin plays an important role in the T-cell receptor-mediated signal transduction pathway. The protein encoded by this gene binds specifically to the activated form of calcineurin and inhibits calcineurin-mediated signal transduction. The encoded protein is found in the nucleus and contains a leucine zipper domain as well as several PEST motifs, sequences which confer targeted degradation to those proteins which contain them. Alternative splicing results in multiple transcript variants encoding two different isoforms. [provided by RefSeq, Jan 2011]

CABIN1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), CABIN1. . Gene score misZ 1.9223 (greater than the threshold 3.09). Trascript score misZ 3.5534 (greater than threshold 3.09). GenCC has associacion of gene with neurofibromatosis.

BP4

Computational evidence support a benign effect (MetaRNN=0.0015768409).

BP6

Variant 22-24050841-G-A is Benign according to our data. Variant chr22-24050841-G-A is described in ClinVar as [Benign]. Clinvar id is 1250878.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0954 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CABIN1	NM_012295.4 linkuse as main transcript	c.673G>A	p.Asp225Asn	missense_variant	8/37	ENST00000263119.10	NP_036427.1	Q9Y6J0-1A0A024R1E5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CABIN1	ENST00000263119.10 linkuse as main transcript	c.673G>A	p.Asp225Asn	missense_variant	8/37	1	NM_012295.4	ENSP00000263119.5		Q9Y6J0-1

Frequencies

GnomAD3 genomes

AF:

0.0412

AC:

6262

AN:

152108

Hom.:

243

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0979

Gnomad AMI

AF:

0.00548

Gnomad AMR

AF:

0.0324

Gnomad ASJ

AF:

0.0207

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00311

Gnomad FIN

AF:

0.0106

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0209

Gnomad OTH

AF:

0.0368

GnomAD3 exomes

AF:

0.0221

AC:

5548

AN:

251454

Hom.:

122

AF XY:

0.0200

AC XY:

2713

AN XY:

135902

show subpopulations

Gnomad AFR exome

AF:

0.103

Gnomad AMR exome

AF:

0.0184

Gnomad ASJ exome

AF:

0.0200

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00454

Gnomad FIN exome

AF:

0.0120

Gnomad NFE exome

AF:

0.0219

Gnomad OTH exome

AF:

0.0238

GnomAD4 exome

AF:

0.0201

AC:

29419

AN:

1461848

Hom.:

470

Cov.:

AF XY:

0.0193

AC XY:

14004

AN XY:

727220

show subpopulations

Gnomad4 AFR exome

AF:

0.103

Gnomad4 AMR exome

AF:

0.0208

Gnomad4 ASJ exome

AF:

0.0198

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00496

Gnomad4 FIN exome

AF:

0.0127

Gnomad4 NFE exome

AF:

0.0197

Gnomad4 OTH exome

AF:

0.0231

GnomAD4 genome

AF:

0.0412

AC:

6271

AN:

152226

Hom.:

243

Cov.:

AF XY:

0.0390

AC XY:

2907

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.0979

Gnomad4 AMR

AF:

0.0324

Gnomad4 ASJ

AF:

0.0207

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00311

Gnomad4 FIN

AF:

0.0106

Gnomad4 NFE

AF:

0.0209

Gnomad4 OTH

AF:

0.0364

Alfa

AF:

0.0248

Hom.:

119

Bravo

AF:

0.0449

TwinsUK

AF:

0.0210

AC:

ALSPAC

AF:

0.0197

AC:

ESP6500AA

AF:

0.0994

AC:

438

ESP6500EA

AF:

0.0187

AC:

161

ExAC

AF:

0.0240

AC:

2913

Asia WGS

AF:

0.00808

AC:

AN:

3478

EpiCase

AF:

0.0191

EpiControl

AF:

0.0210

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 04, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

CABIN1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 05, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.62

CADD

Benign

DANN

Benign

0.62

DEOGEN2

Benign

0.0050

T;T;.;T

Eigen

Benign

-0.96

Eigen_PC

Benign

-0.81

FATHMM_MKL

Benign

0.74

LIST_S2

Uncertain

0.87

D;.;D;D

MetaRNN

Benign

0.0016

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.14

.;N;.;N

PrimateAI

Benign

0.36

PROVEAN

Benign

-0.28

N;N;N;N

REVEL

Benign

0.097

Sift

Benign

0.48

T;T;T;T

Sift4G

Benign

0.88

T;T;T;T

Polyphen

0.0010, 0.0020

.;B;B;B

Vest4

0.091, 0.037

MPC

0.28

ClinPred

0.00069

GERP RS

3.2

Varity_R

0.025

gMVP

0.19

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

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