15-90234035-G-A

Variant names:

• chr15-90234035-G-A
• rs8025979
• ENST00000612800.1:c.-150C>T

Variant summary

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

The ENST00000612800.1(CIB1):​c.-150C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.369 in 897,370 control chromosomes in the GnomAD database, including 63,668 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.36 (10238 hom., cov: 33)
  • Exomes 𝑓: 0.37 (53430 hom.)
• Consequence: CIB1 ENST00000612800.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.18

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]

GDPGP1 (HGNC:34360): (GDP-D-glucose phosphorylase 1) Enables GDP-D-glucose phosphorylase activity. Involved in glucose metabolic process. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000284626 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 15-90234035-G-A is Benign according to our data. Variant chr15-90234035-G-A is described in ClinVar as [Benign]. Clinvar id is 2688441.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.386 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GDPGP1	NM_001013657.3	c.-399G>A		upstream_gene_variant		ENST00000329600.8	NP_001013679.2
CIB1	NM_006384.4	c.-150C>T		upstream_gene_variant		ENST00000328649.11	NP_006375.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GDPGP1	ENST00000329600.8	c.-399G>A		upstream_gene_variant		6	NM_001013657.3	ENSP00000368405.3
CIB1	ENST00000328649.11	c.-150C>T		upstream_gene_variant		1	NM_006384.4	ENSP00000333873.6
ENSG00000284626	ENST00000641199.1	n.-518G>A		upstream_gene_variant				ENSP00000492952.1

Frequencies

GnomAD3 genomes AF: 0.362 AC: 55084 AN: 152018 Hom.: 10242 Cov.: 33

Gnomad AFR AF: 0.368

Gnomad AMI AF: 0.458

Gnomad AMR AF: 0.331

Gnomad ASJ AF: 0.394

Gnomad EAS AF: 0.122

Gnomad SAS AF: 0.258

Gnomad FIN AF: 0.350

Gnomad MID AF: 0.439

Gnomad NFE AF: 0.390

Gnomad OTH AF: 0.383

GnomAD4 exome AF: 0.370 AC: 275675 AN: 745244 Hom.: 53430 Cov.: 10 AF XY: 0.368 AC XY: 136891 AN XY: 372478

Gnomad4 AFR exome AF: 0.365

Gnomad4 AMR exome AF: 0.309

Gnomad4 ASJ exome AF: 0.384

Gnomad4 EAS exome AF: 0.115

Gnomad4 SAS exome AF: 0.273

Gnomad4 FIN exome AF: 0.337

Gnomad4 NFE exome AF: 0.393

Gnomad4 OTH exome AF: 0.370

GnomAD4 genome AF: 0.362 AC: 55108 AN: 152126 Hom.: 10238 Cov.: 33 AF XY: 0.353 AC XY: 26272 AN XY: 74382

Gnomad4 AFR AF: 0.368

Gnomad4 AMR AF: 0.330

Gnomad4 ASJ AF: 0.394

Gnomad4 EAS AF: 0.122

Gnomad4 SAS AF: 0.258

Gnomad4 FIN AF: 0.350

Gnomad4 NFE AF: 0.390

Gnomad4 OTH AF: 0.383

Alfa AF: 0.375 Hom.: 1659

Bravo AF: 0.364

Asia WGS AF: 0.215 AC: 752 AN: 3472

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 39% of patients studied by a panel of primary immunodeficiencies. Number of patients: 34. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	12
DANN	Benign	0.68

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs8025979; hg19: chr15-90777267;