rs10456

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_006383.4(CIB2):c.477C>T(p.Asp159Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.228 in 1,614,016 control chromosomes in the GnomAD database, including 44,678 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.19 ( 3096 hom., cov: 32)

Exomes 𝑓: 0.23 ( 41582 hom. )

Consequence

CIB2
NM_006383.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.392

Publications

23 publications found

Variant links:

Genes affected

CIB2 (HGNC:24579): (calcium and integrin binding family member 2) The protein encoded by this gene is similar to that of KIP/CIB, calcineurin B, and calmodulin. The encoded protein is a calcium-binding regulatory protein that interacts with DNA-dependent protein kinase catalytic subunits (DNA-PKcs), and it is involved in photoreceptor cell maintenance. Mutations in this gene cause deafness, autosomal recessive, 48 (DFNB48), and also Usher syndrome 1J (USH1J). Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]

CIB2 Gene-Disease associations (from GenCC):

nonsyndromic genetic hearing loss
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
Usher syndrome type 1J
Inheritance: Unknown, AR Classification: DEFINITIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P
autosomal recessive nonsyndromic hearing loss 48
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, PanelApp Australia
hearing loss, autosomal recessive
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
Usher syndrome type 1
Inheritance: AR Classification: SUPPORTIVE, NO_KNOWN Submitted by: ClinGen, Orphanet

CIB2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

Variant 15-78105804-G-A is Benign according to our data. Variant chr15-78105804-G-A is described in ClinVar as Benign. ClinVar VariationId is 226517.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.392 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.244 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CIB2	NM_006383.4 link	c.477C>T	p.Asp159Asp	synonymous_variant	Exon 5 of 6	ENST00000258930.8	NP_006374.1	O75838-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CIB2	ENST00000258930.8 link	c.477C>T	p.Asp159Asp	synonymous_variant	Exon 5 of 6	1	NM_006383.4	ENSP00000258930.3		O75838-1

Frequencies

GnomAD3 genomes

AF:

0.186

AC:

28251

AN:

152058

Hom.:

3099

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0778

Gnomad AMI

AF:

0.170

Gnomad AMR

AF:

0.165

Gnomad ASJ

AF:

0.292

Gnomad EAS

AF:

0.0224

Gnomad SAS

AF:

0.153

Gnomad FIN

AF:

0.303

Gnomad MID

AF:

0.206

Gnomad NFE

AF:

0.247

Gnomad OTH

AF:

0.196

GnomAD2 exomes

AF:

0.204

AC:

51300

AN:

251430

AF XY:

0.207

show subpopulations

Gnomad AFR exome

AF:

0.0731

Gnomad AMR exome

AF:

0.164

Gnomad ASJ exome

AF:

0.284

Gnomad EAS exome

AF:

0.0177

Gnomad FIN exome

AF:

0.307

Gnomad NFE exome

AF:

0.248

Gnomad OTH exome

AF:

0.230

GnomAD4 exome

AF:

0.233

AC:

339996

AN:

1461840

Hom.:

41582

Cov.:

AF XY:

0.231

AC XY:

168166

AN XY:

727224

show subpopulations

African (AFR)

AF:

0.0728

AC:

2437

AN:

33480

American (AMR)

AF:

0.166

AC:

7434

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.287

AC:

7504

AN:

26136

East Asian (EAS)

AF:

0.0224

AC:

888

AN:

39700

South Asian (SAS)

AF:

0.162

AC:

14000

AN:

86256

European-Finnish (FIN)

AF:

0.306

AC:

16317

AN:

53410

Middle Eastern (MID)

AF:

0.221

AC:

1277

AN:

5768

European-Non Finnish (NFE)

AF:

0.249

AC:

276624

AN:

1111974

Other (OTH)

AF:

0.224

AC:

13515

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

17334

34668

52003

69337

86671

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9108

18216

27324

36432

45540

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.186

AC:

28240

AN:

152176

Hom.:

3096

Cov.:

AF XY:

0.187

AC XY:

13880

AN XY:

74396

show subpopulations

African (AFR)

AF:

0.0776

AC:

3221

AN:

41528

American (AMR)

AF:

0.165

AC:

2521

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.292

AC:

1014

AN:

3470

East Asian (EAS)

AF:

0.0228

AC:

118

AN:

5176

South Asian (SAS)

AF:

0.152

AC:

733

AN:

4826

European-Finnish (FIN)

AF:

0.303

AC:

3205

AN:

10586

Middle Eastern (MID)

AF:

0.211

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.247

AC:

16803

AN:

67976

Other (OTH)

AF:

0.193

AC:

408

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1183

2365

3548

4730

5913

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

302

604

906

1208

1510

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.223

Hom.:

11843

Bravo

AF:

0.171

Asia WGS

AF:

0.0960

AC:

334

AN:

3478

EpiCase

AF:

0.253

EpiControl

AF:

0.245

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Jun 01, 2017

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Nov 24, 2014

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Asp159Asp in exon 5 of CIB2: This variant is not expected to have clinical signi ficance because it does not alter an amino acid residue and is not located withi n the splice consensus sequence. It has been identified in 24.4% (2095/8586) of European American chromosomes from a broad population by the NHLBI Exome Sequenc ing Project (http://evs.gs.washington.edu/EVS; dbSNP rs10456). -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

0.26

(source)

DANN

Benign

0.80

PhyloP100

-0.39

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over