Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_006383.4(CIB2):c.393G>A(p.Thr131Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0449 in 1,614,138 control chromosomes in the GnomAD database, including 2,682 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.051 ( 301 hom., cov: 32)

Exomes 𝑓: 0.044 ( 2381 hom. )

Consequence

CIB2
NM_006383.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.27

Publications

4 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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.37).

BP6

Variant 15-78105888-C-T is Benign according to our data. Variant chr15-78105888-C-T is described in ClinVar as Benign. ClinVar VariationId is 226516.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.27 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.153 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006383.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
CIB2	NM_006383.4	MANE Select	c.393G>A	p.Thr131Thr	synonymous	Exon 5 of 6	NP_006374.1
CIB2	NM_001301224.2		c.408G>A	p.Thr136Thr	synonymous	Exon 4 of 5	NP_001288153.1
CIB2	NM_001271888.2		c.264G>A	p.Thr88Thr	synonymous	Exon 4 of 5	NP_001258817.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
CIB2	ENST00000258930.8	TSL:1 MANE Select	c.393G>A	p.Thr131Thr	synonymous	Exon 5 of 6	ENSP00000258930.3
CIB2	ENST00000539011.5	TSL:1	c.264G>A	p.Thr88Thr	synonymous	Exon 4 of 5	ENSP00000442459.1
CIB2	ENST00000560618.5	TSL:2	c.264G>A	p.Thr88Thr	synonymous	Exon 4 of 4	ENSP00000452752.1

Frequencies

GnomAD3 genomes

AF:

0.0511

AC:

7774

AN:

152144

Hom.:

303

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0817

Gnomad AMI

AF:

0.00439

Gnomad AMR

AF:

0.0431

Gnomad ASJ

AF:

0.0602

Gnomad EAS

AF:

0.00135

Gnomad SAS

AF:

0.163

Gnomad FIN

AF:

0.0129

Gnomad MID

AF:

0.104

Gnomad NFE

AF:

0.0357

Gnomad OTH

AF:

0.0588

GnomAD2 exomes

AF:

0.0503

AC:

12660

AN:

251446

AF XY:

0.0557

show subpopulations

Gnomad AFR exome

AF:

0.0827

Gnomad AMR exome

AF:

0.0280

Gnomad ASJ exome

AF:

0.0599

Gnomad EAS exome

AF:

0.000544

Gnomad FIN exome

AF:

0.0133

Gnomad NFE exome

AF:

0.0364

Gnomad OTH exome

AF:

0.0508

GnomAD4 exome

AF:

0.0443

AC:

64717

AN:

1461876

Hom.:

2381

Cov.:

AF XY:

0.0475

AC XY:

34573

AN XY:

727238

show subpopulations

African (AFR)

AF:

0.0858

AC:

2871

AN:

33480

American (AMR)

AF:

0.0288

AC:

1288

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0567

AC:

1481

AN:

26134

East Asian (EAS)

AF:

0.000378

AC:

AN:

39700

South Asian (SAS)

AF:

0.158

AC:

13622

AN:

86256

European-Finnish (FIN)

AF:

0.0133

AC:

709

AN:

53418

Middle Eastern (MID)

AF:

0.0915

AC:

528

AN:

5768

European-Non Finnish (NFE)

AF:

0.0370

AC:

41157

AN:

1112000

Other (OTH)

AF:

0.0504

AC:

3046

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

3738

7477

11215

14954

18692

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1712

3424

5136

6848

8560

<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:

0.0510

AC:

7769

AN:

152262

Hom.:

301

Cov.:

AF XY:

0.0510

AC XY:

3800

AN XY:

74446

show subpopulations

African (AFR)

AF:

0.0815

AC:

3385

AN:

41520

American (AMR)

AF:

0.0430

AC:

658

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.0602

AC:

209

AN:

3472

East Asian (EAS)

AF:

0.00135

AC:

AN:

5182

South Asian (SAS)

AF:

0.163

AC:

786

AN:

4824

European-Finnish (FIN)

AF:

0.0129

AC:

137

AN:

10614

Middle Eastern (MID)

AF:

0.0952

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0357

AC:

2432

AN:

68028

Other (OTH)

AF:

0.0582

AC:

123

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

355

709

1064

1418

1773

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

104

208

312

416

520

<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:

0.0357

Hom.:

Bravo

AF:

0.0514

Asia WGS

AF:

0.0870

AC:

303

AN:

3478

EpiCase

AF:

0.0426

EpiControl

AF:

0.0427

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (3)

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.37

CADD

Benign

0.96

(source)

DANN

Benign

0.85

PhyloP100

-1.3

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

NM_006383.4:c.393G>A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over