NM_006384.4:c.20G>T

Variant names:

• chr15-90233866-C-A
• rs1962570345
• NM_006384.4:c.20G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006384.4(CIB1):​c.20G>T​(p.Arg7Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000741 in 1,349,844 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. Variant has been reported in ClinVar as Uncertain significance (★). 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: 7.4e-7 (0 hom.)
• Consequence: CIB1 NM_006384.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.751
• Publications: 0 publications found

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

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=0.12633204).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CIB1	NM_006384.4	MANE Select	c.20G>T	p.Arg7Leu	missense	Exon 1 of 7	NP_006375.2	Q99828-1
	CIB1	NM_001277764.2		c.20G>T	p.Arg7Leu	missense	Exon 1 of 7	NP_001264693.1	Q99828-2
	CIB1	NR_102427.1		n.237+53G>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CIB1	ENST00000328649.11	TSL:1 MANE Select	c.20G>T	p.Arg7Leu	missense	Exon 1 of 7	ENSP00000333873.6	Q99828-1
	CIB1	ENST00000612800.1	TSL:1	c.20G>T	p.Arg7Leu	missense	Exon 1 of 7	ENSP00000479860.1	Q99828-2
	CIB1	ENST00000970526.1		c.20G>T	p.Arg7Leu	missense	Exon 1 of 7	ENSP00000640585.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.41e-7 AC: 1 AN: 1349844 Hom.: 0 Cov.: 32 AF XY: 0.00000151 AC XY: 1 AN XY: 662120

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 29958

American (AMR) AF: 0.00 AC: 0 AN: 29376

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21698

East Asian (EAS) AF: 0.00 AC: 0 AN: 35208

South Asian (SAS) AF: 0.00 AC: 0 AN: 72506

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 42742

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3876

European-Non Finnish (NFE) AF: 9.45e-7 AC: 1 AN: 1058700

Other (OTH) AF: 0.00 AC: 0 AN: 55780

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.40
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.19	T
Eigen	Benign	-0.25
Eigen_PC	Benign	-0.085
FATHMM_MKL	Benign	0.75	D
LIST_S2	Benign	0.74	T
M_CAP	Uncertain	0.15	D
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.90	L
PhyloP100		0.75
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-0.82	N
REVEL	Benign	0.046
Sift	Benign	0.16	T
Sift4G	Benign	0.73	T
Polyphen		0.45	B
Vest4		0.099
MutPred		0.37		Loss of loop (P = 0.0031)
MVP		0.73
MPC		0.21
ClinPred		0.59	D
GERP RS		3.1
PromoterAI		0.027	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.14
gMVP		0.15
Mutation Taster		=68/32	polymorphism

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

Other links and lift over

dbSNP: rs1962570345; hg19: chr15-90777098;