dbSNP rs769387722: CIB1:p.Gly3Val (chr15-90233878-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_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. 13/22 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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.12

Publications

0 publications found

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:

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]

GDPGP1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.22937119).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006384.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CIB1	NM_006384.4	MANE Select	c.8G>T	p.Gly3Val	missense	Exon 1 of 7	NP_006375.2	Q99828-1
CIB1	NM_001277764.2		c.8G>T	p.Gly3Val	missense	Exon 1 of 7	NP_001264693.1	Q99828-2
CIB1	NR_102427.1		n.237+41G>T		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CIB1	ENST00000328649.11	TSL:1 MANE Select	c.8G>T	p.Gly3Val	missense	Exon 1 of 7	ENSP00000333873.6	Q99828-1
CIB1	ENST00000612800.1	TSL:1	c.8G>T	p.Gly3Val	missense	Exon 1 of 7	ENSP00000479860.1	Q99828-2
CIB1	ENST00000970526.1		c.8G>T	p.Gly3Val	missense	Exon 1 of 7	ENSP00000640585.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.57e-7

AC:

AN:

1321488

Hom.:

Cov.:

AF XY:

0.00000155

AC XY:

AN XY:

646070

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

28706

American (AMR)

AF:

0.00

AC:

AN:

24310

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19950

East Asian (EAS)

AF:

0.00

AC:

AN:

34704

South Asian (SAS)

AF:

0.00

AC:

AN:

67816

European-Finnish (FIN)

AF:

0.00

AC:

AN:

39928

Middle Eastern (MID)

AF:

0.000266

AC:

AN:

3754

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1047742

Other (OTH)

AF:

0.00

AC:

AN:

54578

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.625

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.23

BayesDel_addAF

Benign

-0.053

BayesDel_noAF

Benign

-0.31

CADD

Uncertain

(source)

DANN

Benign

0.97

DEOGEN2

Uncertain

0.59

Eigen

Benign

-0.20

Eigen_PC

Benign

-0.045

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.74

M_CAP

Uncertain

0.18

MetaRNN

Benign

0.23

MetaSVM

Benign

-0.89

MutationAssessor

Benign

1.7

PhyloP100

1.1

PrimateAI

Uncertain

0.64

PROVEAN

Uncertain

-2.7

REVEL

Benign

0.086

Sift

Benign

0.27

Sift4G

Benign

0.12

Polyphen

0.050

Vest4

0.24

MutPred

0.18

Loss of catalytic residue at S4 (P = 0.1824)

MVP

0.78

MPC

0.24

ClinPred

0.84

GERP RS

4.4

PromoterAI

-0.0098

Neutral

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over