8-93704978-C-A

Variant names:

• chr8-93704978-C-A
• rs1215667615
• NM_145269.5:c.400C>A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1 PM2

The NM_145269.5(CIBAR1):​c.400C>A​(p.Arg134Ser) variant causes a missense change. 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)
• Consequence: CIBAR1 NM_145269.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.69

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 4 ACMG points.

• PM1: In a mutagenesis_site Reduced membrane-binding and significant reduction in membrane remodeling activity; when associated with A-132 and A-136. (size 0) in uniprot entity CBAR1_HUMAN
• 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.400C>A	p.Arg134Ser	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.400C>A	p.Arg134Ser	missense_variant	Exon 4 of 9	5	NM_145269.5	ENSP00000429367.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000402 AC: 1 AN: 248520 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 134854

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000329

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.97
BayesDel_addAF	Pathogenic	0.30	D
BayesDel_noAF	Pathogenic	0.19
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.16	.;T;T;.;T;.;T;.;.
Eigen	Uncertain	0.56
Eigen_PC	Uncertain	0.61
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.97	D;D;D;D;D;D;D;D;D
M_CAP	Benign	0.035	D
MetaRNN	Uncertain	0.73	D;D;D;D;D;D;D;D;D
MetaSVM	Benign	-1.0	T
PrimateAI	Uncertain	0.72	T
PROVEAN	Pathogenic	-5.3	D;D;D;D;D;D;.;D;D
REVEL	Uncertain	0.41
Sift	Uncertain	0.0010	D;D;D;D;D;D;.;D;D
Sift4G	Uncertain	0.0030	D;D;D;D;D;D;D;D;D
Polyphen		0.99	.;.;D;.;.;.;.;.;.
Vest4		0.94, 0.90, 0.94, 0.96
MutPred		0.54		.;.;Gain of phosphorylation at R134 (P = 0.0203);Gain of phosphorylation at R134 (P = 0.0203);.;Gain of phosphorylation at R134 (P = 0.0203);Gain of phosphorylation at R134 (P = 0.0203);.;.;
MVP		0.77
MPC		0.65
ClinPred		0.99	D
GERP RS		5.7
Varity_R		0.84
gMVP		0.76

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1215667615; hg19: chr8-94717206;