15-90230807-C-T

Variant names:

• chr15-90230807-C-T
• rs2073705
• NM_006384.4:c.554+127G>A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_006384.4(CIB1):​c.554+127G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.281 in 887,354 control chromosomes in the GnomAD database, including 41,888 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.26 (6195 hom., cov: 33)
  • Exomes 𝑓: 0.28 (35693 hom.)
• Consequence: CIB1 NM_006384.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.754

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 15-90230807-C-T is Benign according to our data. Variant chr15-90230807-C-T is described in ClinVar as [Benign]. Clinvar id is 2688000.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.676 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CIB1	NM_006384.4	c.554+127G>A		intron_variant	Intron 6 of 6	ENST00000328649.11	NP_006375.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CIB1	ENST00000328649.11	c.554+127G>A		intron_variant	Intron 6 of 6	1	NM_006384.4	ENSP00000333873.6

Frequencies

GnomAD3 genomes AF: 0.264 AC: 40103 AN: 151982 Hom.: 6186 Cov.: 33

Gnomad AFR AF: 0.200

Gnomad AMI AF: 0.151

Gnomad AMR AF: 0.399

Gnomad ASJ AF: 0.172

Gnomad EAS AF: 0.695

Gnomad SAS AF: 0.423

Gnomad FIN AF: 0.269

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.234

Gnomad OTH AF: 0.273

GnomAD4 exome AF: 0.284 AC: 209135 AN: 735252 Hom.: 35693 AF XY: 0.288 AC XY: 111893 AN XY: 387986

Gnomad4 AFR exome AF: 0.191

Gnomad4 AMR exome AF: 0.506

Gnomad4 ASJ exome AF: 0.186

Gnomad4 EAS exome AF: 0.661

Gnomad4 SAS exome AF: 0.416

Gnomad4 FIN exome AF: 0.273

Gnomad4 NFE exome AF: 0.229

Gnomad4 OTH exome AF: 0.269

GnomAD4 genome AF: 0.264 AC: 40130 AN: 152102 Hom.: 6195 Cov.: 33 AF XY: 0.274 AC XY: 20403 AN XY: 74346

Gnomad4 AFR AF: 0.200

Gnomad4 AMR AF: 0.399

Gnomad4 ASJ AF: 0.172

Gnomad4 EAS AF: 0.695

Gnomad4 SAS AF: 0.423

Gnomad4 FIN AF: 0.269

Gnomad4 NFE AF: 0.234

Gnomad4 OTH AF: 0.272

Alfa AF: 0.240 Hom.: 732

Bravo AF: 0.269

Asia WGS AF: 0.508 AC: 1765 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

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 74% 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	-0.86
CADD	Benign	0.63
DANN	Benign	0.55

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

Other links and lift over

dbSNP: rs2073705; hg19: chr15-90774039;