NM_145269.5:c.800A>C

Variant names:

• chr8-93728227-A-C
• rs533013204
• NM_145269.5:c.800A>C

Variant summary

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

The NM_145269.5(CIBAR1):​c.800A>C​(p.Lys267Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000126 in 1,593,348 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. K267R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: CIBAR1 NM_145269.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.27
• Publications: 0 publications found

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]

RBM12B (HGNC:32310): (RNA binding motif protein 12B) Enables RNA binding activity. Predicted to be involved in regulation of RNA splicing. Predicted to be part of ribonucleoprotein complex. Predicted to be active in nucleoplasm. [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=0.21256807).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145269.5. 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
	CIBAR1	NM_145269.5	MANE Select	c.800A>C	p.Lys267Thr	missense	Exon 9 of 9	NP_660312.2	A1XBS5-1
	RBM12B	NM_001377960.1	MANE Select	c.*5178T>G		3_prime_UTR	Exon 4 of 4	NP_001364889.1	Q8IXT5
	CIBAR1	NM_001283034.2		c.686A>C	p.Lys229Thr	missense	Exon 8 of 8	NP_001269963.1	A1XBS5-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CIBAR1	ENST00000518322.6	TSL:5 MANE Select	c.800A>C	p.Lys267Thr	missense	Exon 9 of 9	ENSP00000429367.1	A1XBS5-1
	RBM12B	ENST00000520560.6	TSL:2 MANE Select	c.*5178T>G		3_prime_UTR	Exon 4 of 4	ENSP00000429807.2	Q8IXT5
	RBM12B	ENST00000517700.6	TSL:1	c.*5178T>G		3_prime_UTR	Exon 3 of 3	ENSP00000427729.2	Q8IXT5

Frequencies

GnomAD3 genomes AF: 0.00000660 AC: 1 AN: 151630 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000196

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 6.94e-7 AC: 1 AN: 1441718 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 716532

African (AFR) AF: 0.00 AC: 0 AN: 32392

American (AMR) AF: 0.00 AC: 0 AN: 40718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25760

East Asian (EAS) AF: 0.0000258 AC: 1 AN: 38764

South Asian (SAS) AF: 0.00 AC: 0 AN: 81408

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53154

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4190

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1105836

Other (OTH) AF: 0.00 AC: 0 AN: 59496

GnomAD4 genome AF: 0.00000660 AC: 1 AN: 151630 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74006

African (AFR) AF: 0.00 AC: 0 AN: 41254

American (AMR) AF: 0.00 AC: 0 AN: 15208

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000196 AC: 1 AN: 5112

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10502

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67950

Other (OTH) AF: 0.00 AC: 0 AN: 2084

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.052	T
BayesDel_noAF	Benign	-0.31
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0071	T
Eigen	Uncertain	0.41
Eigen_PC	Uncertain	0.40
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.85	D
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-0.77	T
PhyloP100		3.3
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.14
Sift	Uncertain	0.0080	D
Sift4G	Benign	0.28	T
Polyphen		0.97	D
Vest4		0.30
MutPred		0.19		Loss of ubiquitination at K267 (P = 8e-04)
MVP		0.74
MPC		0.50
ClinPred		0.93	D
GERP RS		4.3
Varity_R		0.12
gMVP		0.11
Mutation Taster		=76/24	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: rs533013204; hg19: chr8-94740455;