Variant NM_006384.4:c.555-45G>A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_006384.4(CIB1):c.555-45G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.501 in 1,548,520 control chromosomes in the GnomAD database, including 199,009 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.49 ( 18632 hom., cov: 32)

Exomes 𝑓: 0.50 ( 180377 hom. )

Consequence

CIB1
NM_006384.4 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.65

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 15-90230550-C-T is Benign according to our data. Variant chr15-90230550-C-T is described in ClinVar as [Benign]. Clinvar id is 2688352.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.795 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
CIB1	NM_006384.4 link	c.555-45G>A	intron_variant	Intron 6 of 6	ENST00000328649.11	NP_006375.2	Q99828-1A0A140VK09
CIB1	NM_001277764.2 link	c.675-45G>A	intron_variant	Intron 6 of 6		NP_001264693.1	Q99828-2
CIB1	NR_102427.1 link	n.741-45G>A	intron_variant	Intron 6 of 6
CIB1	NR_102428.1 link	n.607-45G>A	intron_variant	Intron 6 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CIB1	ENST00000328649.11 link	c.555-45G>A		intron_variant	Intron 6 of 6	1	NM_006384.4	ENSP00000333873.6		Q99828-1

Frequencies

GnomAD3 genomes

AF:

0.487

AC:

73946

AN:

151900

Hom.:

18621

Cov.:

show subpopulations

Gnomad AFR

AF:

0.391

Gnomad AMI

AF:

0.394

Gnomad AMR

AF:

0.585

Gnomad ASJ

AF:

0.453

Gnomad EAS

AF:

0.815

Gnomad SAS

AF:

0.641

Gnomad FIN

AF:

0.534

Gnomad MID

AF:

0.487

Gnomad NFE

AF:

0.482

Gnomad OTH

AF:

0.491

GnomAD3 exomes

AF:

0.555

AC:

86289

AN:

155574

Hom.:

25059

AF XY:

0.559

AC XY:

45794

AN XY:

81904

show subpopulations

Gnomad AFR exome

AF:

0.377

Gnomad AMR exome

AF:

0.650

Gnomad ASJ exome

AF:

0.461

Gnomad EAS exome

AF:

0.824

Gnomad SAS exome

AF:

0.643

Gnomad FIN exome

AF:

0.539

Gnomad NFE exome

AF:

0.476

Gnomad OTH exome

AF:

0.520

GnomAD4 exome

AF:

0.503

AC:

702442

AN:

1396502

Hom.:

180377

Cov.:

AF XY:

0.507

AC XY:

349286

AN XY:

688972

show subpopulations

Gnomad4 AFR exome

AF:

0.382

Gnomad4 AMR exome

AF:

0.641

Gnomad4 ASJ exome

AF:

0.457

Gnomad4 EAS exome

AF:

0.775

Gnomad4 SAS exome

AF:

0.638

Gnomad4 FIN exome

AF:

0.535

Gnomad4 NFE exome

AF:

0.482

Gnomad4 OTH exome

AF:

0.509

GnomAD4 genome

AF:

0.487

AC:

73989

AN:

152018

Hom.:

18632

Cov.:

AF XY:

0.497

AC XY:

36918

AN XY:

74310

show subpopulations

Gnomad4 AFR

AF:

0.391

Gnomad4 AMR

AF:

0.586

Gnomad4 ASJ

AF:

0.453

Gnomad4 EAS

AF:

0.816

Gnomad4 SAS

AF:

0.641

Gnomad4 FIN

AF:

0.534

Gnomad4 NFE

AF:

0.482

Gnomad4 OTH

AF:

0.494

Alfa

AF:

0.474

Hom.:

3175

Bravo

AF:

0.481

Asia WGS

AF:

0.692

AC:

2403

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 80% of patients studied by a panel of primary immunodeficiencies. Number of patients: 70. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.11

DANN

Benign

0.71

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