8-93704949-C-G

Variant names:

• chr8-93704949-C-G
• rs201566211
• NM_145269.5:c.371C>G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_145269.5(CIBAR1):​c.371C>G​(p.Ala124Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,459,060 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: CIBAR1 NM_145269.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.01

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.

• PM2: Very rare variant in population databases, with high coverage
• PP3: Splicing scoreres supports a deletorius effect: Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CIBAR1	NM_145269.5	c.371C>G	p.Ala124Gly	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.371C>G	p.Ala124Gly	missense_variant	Exon 4 of 9	5	NM_145269.5	ENSP00000429367.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000404 AC: 1 AN: 247248 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 134184

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: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000889

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459060 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 725730

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: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.070
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.071	.;T;T;.;T;.;T;.;.
Eigen	Uncertain	0.50
Eigen_PC	Uncertain	0.58
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.67	T;T;T;T;T;T;T;T;D
M_CAP	Benign	0.013	T
MetaRNN	Uncertain	0.62	D;D;D;D;D;D;D;D;D
MetaSVM	Benign	-0.48	T
PrimateAI	Uncertain	0.57	T
PROVEAN	Uncertain	-3.1	D;D;D;D;D;D;.;D;D
REVEL	Benign	0.27
Sift	Uncertain	0.0080	D;D;D;D;D;D;.;D;D
Sift4G	Benign	0.16	T;T;D;D;D;D;D;T;D
Polyphen		0.97	.;.;D;.;.;.;.;.;.
Vest4		0.69, 0.47, 0.71
MutPred		0.56		.;.;Loss of helix (P = 0.0444);Loss of helix (P = 0.0444);.;Loss of helix (P = 0.0444);Loss of helix (P = 0.0444);.;.;
MVP		0.81
MPC		0.15
ClinPred		0.87	D
GERP RS		5.7
Varity_R		0.52
gMVP		0.38

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.98		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.98		Position offset: -1

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs201566211; hg19: chr8-94717177;