chr8-93704942-C-G

Variant names:

• chr8-93704942-C-G
• rs373275688
• NM_145269.5:c.364C>G

Variant summary

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

The NM_145269.5(CIBAR1):​c.364C>G​(p.Arg122Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CIBAR1 NM_145269.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.99

Genes affected

CIBAR1 (HGNC:30452): (CBY1 interacting BAR domain containing 1) Enables phospholipid binding activity. Involved in several processes, including inner mitochondrial membrane organization; limb morphogenesis; and membrane tubulation. Located in several cellular components, including centriole; ciliary base; and mitochondrial crista. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CIBAR1	NM_145269.5	c.364C>G	p.Arg122Gly	missense_variant	Exon 4 of 9	ENST00000518322.6	NP_660312.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CIBAR1	ENST00000518322.6	c.364C>G	p.Arg122Gly	missense_variant	Exon 4 of 9	5	NM_145269.5	ENSP00000429367.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1458166 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 725240

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.: 32

ExAC AF: 0.00000828 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.86
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.16	.;T;T;.;T;.;T;.;.
Eigen	Uncertain	0.43
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.95	D;D;D;D;D;D;D;D;D
M_CAP	Benign	0.026	D
MetaRNN	Uncertain	0.58	D;D;D;D;D;D;D;D;D
MetaSVM	Benign	-0.36	T
PrimateAI	Uncertain	0.67	T
PROVEAN	Pathogenic	-4.6	D;D;D;D;D;D;.;D;D
REVEL	Benign	0.28
Sift	Uncertain	0.0090	D;D;D;D;D;D;.;D;D
Sift4G	Uncertain	0.025	D;D;D;D;D;D;D;D;D
Polyphen		0.98	.;.;D;.;.;.;.;.;.
Vest4		0.92, 0.76, 0.89, 0.91
MutPred		0.57		.;.;Gain of ubiquitination at K125 (P = 0.0132);Gain of ubiquitination at K125 (P = 0.0132);.;Gain of ubiquitination at K125 (P = 0.0132);Gain of ubiquitination at K125 (P = 0.0132);.;.;
MVP		0.67
MPC		0.57
ClinPred		1.0	D
GERP RS		5.7
Varity_R		0.55
gMVP		0.66

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

LitVar

Other links and lift over

dbSNP: rs373275688; hg19: chr8-94717170;