Genetic Variant CIB1:p.Arg7His (chr15-90233866-C-T) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_006384.4(CIB1):c.20G>A(p.Arg7His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts 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. R7C) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CIB1
NM_006384.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.751

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 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

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.20G>A	p.Arg7His	missense	Exon 1 of 7	NP_006375.2	Q99828-1
CIB1	NM_001277764.2		c.20G>A	p.Arg7His	missense	Exon 1 of 7	NP_001264693.1	Q99828-2
CIB1	NR_102427.1		n.237+53G>A		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CIB1	ENST00000328649.11	TSL:1 MANE Select	c.20G>A	p.Arg7His	missense	Exon 1 of 7	ENSP00000333873.6	Q99828-1
CIB1	ENST00000612800.1	TSL:1	c.20G>A	p.Arg7His	missense	Exon 1 of 7	ENSP00000479860.1	Q99828-2
CIB1	ENST00000970526.1		c.20G>A	p.Arg7His	missense	Exon 1 of 7	ENSP00000640585.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1349842

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

662118

African (AFR)

AF:

0.00

AC:

AN:

29958

American (AMR)

AF:

0.00

AC:

AN:

29376

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21698

East Asian (EAS)

AF:

0.00

AC:

AN:

35208

South Asian (SAS)

AF:

0.00

AC:

AN:

72506

European-Finnish (FIN)

AF:

0.00

AC:

AN:

42742

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3876

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1058698

Other (OTH)

AF:

0.00

AC:

AN:

55780

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Benign

-0.074

BayesDel_noAF

Benign

-0.34

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.27

Eigen

Benign

-0.29

Eigen_PC

Benign

-0.10

FATHMM_MKL

Uncertain

0.76

LIST_S2

Benign

0.79

M_CAP

Uncertain

0.15

MetaRNN

Benign

0.12

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.0

PhyloP100

0.75

PrimateAI

Uncertain

0.68

PROVEAN

Benign

-0.72

REVEL

Benign

0.050

Sift

Benign

0.14

Sift4G

Benign

0.59

Polyphen

0.013

Vest4

0.041

MutPred

0.32

Gain of methylation at K10 (P = 0.0573)

MVP

0.69

MPC

0.21

ClinPred

0.64

GERP RS

3.1

PromoterAI

-0.086

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.082

gMVP

0.11

Mutation Taster

=73/27

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.94

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.94

Position offset: -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