Variant 15-90231027-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_006384.4(CIB1):c.466-5C>G variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.268 in 1,613,294 control chromosomes in the GnomAD database, including 66,588 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.26 ( 6162 hom., cov: 32)

Exomes 𝑓: 0.27 ( 60426 hom. )

Consequence

CIB1
NM_006384.4 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.002671

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.323

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.73).

BP6

Variant 15-90231027-G-C is Benign according to our data. Variant chr15-90231027-G-C is described in ClinVar as [Benign]. Clinvar id is 1167687.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.675 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CIB1	NM_006384.4 linkuse as main transcript	c.466-5C>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000328649.11	NP_006375.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CIB1	ENST00000328649.11 linkuse as main transcript	c.466-5C>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_006384.4	ENSP00000333873	P1	Q99828-1

Frequencies

GnomAD3 genomes

AF:

0.262

AC:

39822

AN:

152036

Hom.:

6154

Cov.:

show subpopulations

Gnomad AFR

AF:

0.188

Gnomad AMI

AF:

0.151

Gnomad AMR

AF:

0.398

Gnomad ASJ

AF:

0.180

Gnomad EAS

AF:

0.693

Gnomad SAS

AF:

0.449

Gnomad FIN

AF:

0.272

Gnomad MID

AF:

0.187

Gnomad NFE

AF:

0.234

Gnomad OTH

AF:

0.274

GnomAD3 exomes

AF:

0.336

AC:

84388

AN:

251272

Hom.:

17495

AF XY:

0.332

AC XY:

45152

AN XY:

135826

show subpopulations

Gnomad AFR exome

AF:

0.188

Gnomad AMR exome

AF:

0.525

Gnomad ASJ exome

AF:

0.193

Gnomad EAS exome

AF:

0.707

Gnomad SAS exome

AF:

0.445

Gnomad FIN exome

AF:

0.276

Gnomad NFE exome

AF:

0.236

Gnomad OTH exome

AF:

0.288

GnomAD4 exome

AF:

0.269

AC:

392589

AN:

1461140

Hom.:

60426

Cov.:

AF XY:

0.273

AC XY:

198261

AN XY:

726904

show subpopulations

Gnomad4 AFR exome

AF:

0.181

Gnomad4 AMR exome

AF:

0.510

Gnomad4 ASJ exome

AF:

0.191

Gnomad4 EAS exome

AF:

0.666

Gnomad4 SAS exome

AF:

0.439

Gnomad4 FIN exome

AF:

0.277

Gnomad4 NFE exome

AF:

0.236

Gnomad4 OTH exome

AF:

0.274

GnomAD4 genome

AF:

0.262

AC:

39844

AN:

152154

Hom.:

6162

Cov.:

AF XY:

0.273

AC XY:

20332

AN XY:

74386

show subpopulations

Gnomad4 AFR

AF:

0.188

Gnomad4 AMR

AF:

0.399

Gnomad4 ASJ

AF:

0.180

Gnomad4 EAS

AF:

0.694

Gnomad4 SAS

AF:

0.449

Gnomad4 FIN

AF:

0.272

Gnomad4 NFE

AF:

0.234

Gnomad4 OTH

AF:

0.273

Alfa

AF:

0.234

Hom.:

1433

Bravo

AF:

0.266

Asia WGS

AF:

0.515

AC:

1789

AN:

3478

EpiCase

AF:

0.224

EpiControl

AF:

0.228

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jan 24, 2024

This variant is classified as Benign based on local population frequency. This variant was detected in 64% of patients studied by a panel of primary immunodeficiencies. Number of patients: 56. Only high quality variants are reported. -

CIB1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 18, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

8.6

DANN

Benign

0.81

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0027

dbscSNV1_RF

Benign

0.054

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