Variant chr15-90230494-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_006384.4(CIB1):c.566T>C(p.Ile189Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00001 in 1,399,358 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

CIB1
NM_006384.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.78

Variant links:

Genes affected

CIB1 (HGNC:16920): (calcium and integrin binding 1) This gene encodes a member of the EF-hand domain-containing calcium-binding superfamily. The encoded protein interacts with many other proteins, including the platelet integrin alpha-IIb-beta-3, DNA-dependent protein kinase, presenilin-2, focal adhesion kinase, p21 activated kinase, and protein kinase D. The encoded protein may be involved in cell survival and proliferation, and is associated with several disease states including cancer and Alzheimer's disease. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2013]

CIB1 links:

CIB1 (HGNC:):

CIB1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CIB1	NM_006384.4 linkuse as main transcript	c.566T>C	p.Ile189Thr	missense_variant	7/7	ENST00000328649.11	NP_006375.2	Q99828-1A0A140VK09
CIB1	NM_001277764.2 linkuse as main transcript	c.686T>C	p.Ile229Thr	missense_variant	7/7		NP_001264693.1	Q99828-2
CIB1	NR_102427.1 linkuse as main transcript	n.752T>C		non_coding_transcript_exon_variant	7/7
CIB1	NR_102428.1 linkuse as main transcript	n.618T>C		non_coding_transcript_exon_variant	7/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CIB1	ENST00000328649.11 linkuse as main transcript	c.566T>C	p.Ile189Thr	missense_variant	7/7	1	NM_006384.4	ENSP00000333873.6		Q99828-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000639

AC:

AN:

156400

Hom.:

AF XY:

0.00

AC XY:

AN XY:

82280

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:

0.0000439

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000100

AC:

AN:

1399358

Hom.:

Cov.:

AF XY:

0.00000869

AC XY:

AN XY:

690182

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:

0.0000126

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000111

Gnomad4 OTH exome

AF:

0.0000172

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000281

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 30, 2022

The c.566T>C (p.I189T) alteration is located in exon 7 (coding exon 7) of the CIB1 gene. This alteration results from a T to C substitution at nucleotide position 566, causing the isoleucine (I) at amino acid position 189 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.96

BayesDel_addAF

Uncertain

0.078

BayesDel_noAF

Uncertain

0.0

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.75

D;.;.

Eigen

Pathogenic

0.69

Eigen_PC

Pathogenic

0.67

FATHMM_MKL

Uncertain

0.81

LIST_S2

Uncertain

0.92

D;D;D

M_CAP

Benign

0.022

MetaRNN

Uncertain

0.71

D;D;D

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.6

M;.;.

MutationTaster

Benign

1.0

PrimateAI

Pathogenic

0.80

PROVEAN

Uncertain

-4.2

D;.;.

REVEL

Uncertain

0.38

Sift

Uncertain

0.0010

D;.;.

Sift4G

Uncertain

0.0020

D;D;.

Polyphen

1.0

D;.;.

Vest4

0.71

MutPred

0.68

Loss of stability (P = 0.0043);.;.;

MVP

0.50

MPC

0.74

ClinPred

0.97

GERP RS

5.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.72

gMVP

0.67

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