Variant 15-78105804-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_006383.4(CIB2):c.477C>T(p.Asp159=) 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

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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/exons	MANE	UniProt
CIB2	NM_006383.4 linkuse as main transcript	c.477C>T	p.Asp159=	synonymous_variant	5/6	ENST00000258930.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CIB2	ENST00000258930.8 linkuse as main transcript	c.477C>T	p.Asp159=	synonymous_variant	5/6	1	NM_006383.4	P1	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

GnomAD3 exomes

AF:

0.204

AC:

51300

AN:

251430

Hom.:

5990

AF XY:

0.207

AC XY:

28103

AN XY:

135882

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 SAS exome

AF:

0.164

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

Gnomad4 AFR exome

AF:

0.0728

Gnomad4 AMR exome

AF:

0.166

Gnomad4 ASJ exome

AF:

0.287

Gnomad4 EAS exome

AF:

0.0224

Gnomad4 SAS exome

AF:

0.162

Gnomad4 FIN exome

AF:

0.306

Gnomad4 NFE exome

AF:

0.249

Gnomad4 OTH exome

AF:

0.224

GnomAD4 genome

AF:

0.186

AC:

28240

AN:

152176

Hom.:

3096

Cov.:

AF XY:

0.187

AC XY:

13880

AN XY:

74396

show subpopulations

Gnomad4 AFR

AF:

0.0776

Gnomad4 AMR

AF:

0.165

Gnomad4 ASJ

AF:

0.292

Gnomad4 EAS

AF:

0.0228

Gnomad4 SAS

AF:

0.152

Gnomad4 FIN

AF:

0.303

Gnomad4 NFE

AF:

0.247

Gnomad4 OTH

AF:

0.193

Alfa

AF:

0.231

Hom.:

5367

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

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 01, 2017	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. -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Nov 24, 2014	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). -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

0.26

DANN

Benign

0.80

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

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