Variant 15-78105126-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_006383.4(CIB2):c.*185C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0199 in 772,342 control chromosomes in the GnomAD database, including 217 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.016 ( 19 hom., cov: 32)

Exomes 𝑓: 0.021 ( 198 hom. )

Consequence

CIB2
NM_006383.4 3_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.493

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 15-78105126-G-C is Benign according to our data. Variant chr15-78105126-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 1179220.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0156 (2373/152118) while in subpopulation NFE AF= 0.0239 (1626/67964). AF 95% confidence interval is 0.023. There are 19 homozygotes in gnomad4. There are 1096 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 19 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CIB2	NM_006383.4 linkuse as main transcript	c.*185C>G		3_prime_UTR_variant	6/6	ENST00000258930.8

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CIB2	ENST00000258930.8 linkuse as main transcript	c.*185C>G	3_prime_UTR_variant	6/6	1	NM_006383.4	P1	O75838-1
CIB2	ENST00000539011.5 linkuse as main transcript	c.*185C>G	3_prime_UTR_variant	5/5	1			O75838-3
CIB2	ENST00000557846.5 linkuse as main transcript	c.*185C>G	3_prime_UTR_variant	4/4	3			O75838-4
CIB2	ENST00000643268.1 linkuse as main transcript		downstream_gene_variant

Frequencies

GnomAD3 genomes

AF:

0.0156

AC:

2373

AN:

152000

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00430

Gnomad AMI

AF:

0.00548

Gnomad AMR

AF:

0.0194

Gnomad ASJ

AF:

0.0297

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0141

Gnomad FIN

AF:

0.00387

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.0239

Gnomad OTH

AF:

0.0225

GnomAD4 exome

AF:

0.0210

AC:

12995

AN:

620224

Hom.:

198

Cov.:

AF XY:

0.0208

AC XY:

6660

AN XY:

319798

show subpopulations

Gnomad4 AFR exome

AF:

0.00448

Gnomad4 AMR exome

AF:

0.0169

Gnomad4 ASJ exome

AF:

0.0276

Gnomad4 EAS exome

AF:

0.0000328

Gnomad4 SAS exome

AF:

0.0169

Gnomad4 FIN exome

AF:

0.00555

Gnomad4 NFE exome

AF:

0.0244

Gnomad4 OTH exome

AF:

0.0229

GnomAD4 genome

AF:

0.0156

AC:

2373

AN:

152118

Hom.:

Cov.:

AF XY:

0.0147

AC XY:

1096

AN XY:

74372

show subpopulations

Gnomad4 AFR

AF:

0.00429

Gnomad4 AMR

AF:

0.0194

Gnomad4 ASJ

AF:

0.0297

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0141

Gnomad4 FIN

AF:

0.00387

Gnomad4 NFE

AF:

0.0239

Gnomad4 OTH

AF:

0.0223

Alfa

AF:

0.0104

Hom.:

Bravo

AF:

0.0174

Asia WGS

AF:

0.00318

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Dec 21, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

4.5

DANN

Benign

0.72

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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