Variant rs145415848 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM1PM2PP5

The NM_006383.4(CIB2):c.192G>C(p.Glu64Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,652 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as not provided (no stars).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

CIB2
NM_006383.4 missense

Scores

Clinical Significance

not provided no classification provided P:1O:2

Conservation

PhyloP100: 1.68

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 Uncertain_significance. Variant got 5 ACMG points.

PM1

In a chain Calcium and integrin-binding family member 2 (size 186) in uniprot entity CIB2_HUMAN there are 10 pathogenic changes around while only 0 benign (100%) in NM_006383.4

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 15-78111171-C-G is Pathogenic according to our data. Variant chr15-78111171-C-G is described in ClinVar as [not_provided]. Clinvar id is 39688.We mark this variant Likely_pathogenic, oryginal submissions are: {not_provided=2, Pathogenic=1}. Variant chr15-78111171-C-G is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CIB2	NM_006383.4 linkuse as main transcript	c.192G>C	p.Glu64Asp	missense_variant	3/6	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.192G>C	p.Glu64Asp	missense_variant	3/6	1	NM_006383.4	ENSP00000258930	P1	O75838-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251356

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135850

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461652

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727120

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: not provided

Submissions summary: Pathogenic:1Other:2

Revision: no classification provided

LINK: link

Submissions by phenotype

Usher syndrome type 1J

Pathogenic:1Other:1

Pathogenic, flagged submission	literature only	OMIM	Nov 01, 2012	- -
not provided, no classification provided	literature only	GeneReviews	-	- -

Usher syndrome type 1

Other:1

not provided, no classification provided

literature only

GeneReviews

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.99

BayesDel_addAF

Pathogenic

0.22

BayesDel_noAF

Pathogenic

0.18

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.27

T;.;.;.;.

Eigen

Uncertain

0.63

Eigen_PC

Uncertain

0.54

FATHMM_MKL

Uncertain

0.95

LIST_S2

Pathogenic

0.98

D;D;D;D;D

M_CAP

Uncertain

0.20

MetaRNN

Uncertain

0.66

D;D;D;D;D

MetaSVM

Uncertain

0.11

MutationAssessor

Uncertain

2.8

M;.;.;.;.

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Uncertain

0.58

PROVEAN

Uncertain

-3.0

D;D;D;D;D

REVEL

Uncertain

0.40

Sift

Pathogenic

0.0

D;D;D;D;D

Sift4G

Uncertain

0.054

T;D;.;D;.

Polyphen

1.0

D;.;.;.;.

Vest4

0.84

MutPred

0.57

Loss of loop (P = 0.1242);.;Loss of loop (P = 0.1242);.;.;

MVP

0.89

MPC

0.22

ClinPred

0.98

GERP RS

3.8

Varity_R

0.75

gMVP

0.73

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