rs117153558

Positions:

chr15-78105819-C-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The ENST00000258930.8(CIB2):c.462G>A(p.Glu154=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0034 in 1,614,212 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0023 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0035 ( 15 hom. )

Consequence

CIB2
ENST00000258930.8 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 0.917

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.27).

BP6

Variant 15-78105819-C-T is Benign according to our data. Variant chr15-78105819-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 197786.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-78105819-C-T is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=0.917 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00232 (354/152340) while in subpopulation NFE AF= 0.0042 (286/68038). AF 95% confidence interval is 0.0038. There are 1 homozygotes in gnomad4. There are 141 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 15 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CIB2	NM_006383.4 linkuse as main transcript	c.462G>A	p.Glu154=	synonymous_variant	5/6	ENST00000258930.8	NP_006374.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CIB2	ENST00000258930.8 linkuse as main transcript	c.462G>A	p.Glu154=	synonymous_variant	5/6	1	NM_006383.4	ENSP00000258930	P1	O75838-1

Frequencies

GnomAD3 genomes

AF:

0.00232

AC:

353

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000603

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00131

Gnomad ASJ

AF:

0.000865

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.000847

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00419

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00221

AC:

555

AN:

251474

Hom.:

AF XY:

0.00240

AC XY:

326

AN XY:

135908

show subpopulations

Gnomad AFR exome

AF:

0.000984

Gnomad AMR exome

AF:

0.000896

Gnomad ASJ exome

AF:

0.00109

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00229

Gnomad FIN exome

AF:

0.000739

Gnomad NFE exome

AF:

0.00350

Gnomad OTH exome

AF:

0.00212

GnomAD4 exome

AF:

0.00351

AC:

5135

AN:

1461872

Hom.:

Cov.:

AF XY:

0.00353

AC XY:

2565

AN XY:

727236

show subpopulations

Gnomad4 AFR exome

AF:

0.000777

Gnomad4 AMR exome

AF:

0.000872

Gnomad4 ASJ exome

AF:

0.00126

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00282

Gnomad4 FIN exome

AF:

0.000543

Gnomad4 NFE exome

AF:

0.00411

Gnomad4 OTH exome

AF:

0.00303

GnomAD4 genome

AF:

0.00232

AC:

354

AN:

152340

Hom.:

Cov.:

AF XY:

0.00189

AC XY:

141

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.000601

Gnomad4 AMR

AF:

0.00131

Gnomad4 ASJ

AF:

0.000865

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00124

Gnomad4 FIN

AF:

0.000847

Gnomad4 NFE

AF:

0.00420

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00286

Hom.:

Bravo

AF:

0.00233

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00414

EpiControl

AF:

0.00391

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:5

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jun 01, 2023	CIB2: BP4, BP7 -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Aug 30, 2018	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 28, 2020	- -

not specified

Benign:3

Likely benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Nov 10, 2014	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Nov 24, 2014	Glu154Glu 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 0.4% (34/8586) of Eur opean American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS; dbSNP rs117153558). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.27

CADD

Benign

7.3

DANN

Benign

0.85

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