15-90230550-C-T

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

2

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]

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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 HGVSp Effect #exon/exons MANE Protein UniProt
CIB1NM_006384.4 linkuse as main transcriptc.555-45G>A intron_variant ENST00000328649.11 NP_006375.2
CIB1NM_001277764.2 linkuse as main transcriptc.675-45G>A intron_variant NP_001264693.1
CIB1NR_102427.1 linkuse as main transcriptn.741-45G>A intron_variant, non_coding_transcript_variant
CIB1NR_102428.1 linkuse as main transcriptn.607-45G>A intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CIB1ENST00000328649.11 linkuse as main transcriptc.555-45G>A intron_variant 1 NM_006384.4 ENSP00000333873 P1Q99828-1

Frequencies

GnomAD3 genomes
AF:
0.487
AC:
73946
AN:
151900
Hom.:
18621
Cov.:
32
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.:
32
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.:
32
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
Benign, criteria provided, single submitterclinical testingUnidad de Genómica Garrahan, Hospital de Pediatría GarrahanJan 24, 2024This 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.

Other links and lift over

dbSNP: rs2073706; hg19: chr15-90773782; COSMIC: COSV60173761; COSMIC: COSV60173761; API