15-90233878-C-A

Variant names:

• chr15-90233878-C-A
• NM_006384.4:c.8G>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006384.4(CIB1):​c.8G>T​(p.Gly3Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000757 in 1,321,488 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G3D) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.6e-7 (0 hom.)
• Consequence: CIB1 NM_006384.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.12

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22937119).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CIB1	NM_006384.4	c.8G>T	p.Gly3Val	missense_variant	Exon 1 of 7	ENST00000328649.11	NP_006375.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CIB1	ENST00000328649.11	c.8G>T	p.Gly3Val	missense_variant	Exon 1 of 7	1	NM_006384.4	ENSP00000333873.6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.57e-7 AC: 1 AN: 1321488 Hom.: 0 Cov.: 32 AF XY: 0.00000155 AC XY: 1 AN XY: 646070

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.053	T
BayesDel_noAF	Benign	-0.31
CADD	Uncertain	23
DANN	Benign	0.97
DEOGEN2	Uncertain	0.59	D;.
Eigen	Benign	-0.20
Eigen_PC	Benign	-0.045
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.74	T;T
M_CAP	Uncertain	0.18	D
MetaRNN	Benign	0.23	T;T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	1.7	L;L
PrimateAI	Uncertain	0.64	T
PROVEAN	Uncertain	-2.7	D;.
REVEL	Benign	0.086
Sift	Benign	0.27	T;.
Sift4G	Benign	0.12	T;T
Polyphen		0.050	B;.
Vest4		0.24
MutPred		0.18		Loss of catalytic residue at S4 (P = 0.1824);Loss of catalytic residue at S4 (P = 0.1824);
MVP		0.78
MPC		0.24
ClinPred		0.84	D
GERP RS		4.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.36
gMVP		0.28

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-90777110;