dbSNP rs533013204: CIBAR1:p.Lys267Thr (chr8-93728227-A-C) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM1PM2BP4_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.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

CIBAR1
NM_145269.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.27

Variant links:

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]

CIBAR1 links:

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]

RBM12B links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM1

In a mutagenesis_site Reduced membrane-binding and significant reduction in membrane remodeling activity; when associated with A-264 and A-266. (size 0) in uniprot entity CBAR1_HUMAN

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.21256807).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CIBAR1	NM_145269.5 link	c.800A>C	p.Lys267Thr	missense_variant	Exon 9 of 9	ENST00000518322.6	NP_660312.2	A1XBS5-1
RBM12B	NM_001377960.1 link	c.*5178T>G		3_prime_UTR_variant	Exon 4 of 4	ENST00000520560.6	NP_001364889.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CIBAR1	ENST00000518322.6 link	c.800A>C	p.Lys267Thr	missense_variant	Exon 9 of 9	5	NM_145269.5	ENSP00000429367.1		A1XBS5-1
RBM12B	ENST00000520560 link	c.*5178T>G		3_prime_UTR_variant	Exon 4 of 4	2	NM_001377960.1	ENSP00000429807.2		Q8IXT5E5RHG1

Frequencies

GnomAD3 genomes

AF:

0.00000660

AC:

AN:

151630

Hom.:

Cov.:

show subpopulations

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:

AN:

1441718

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

716532

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000258

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

AF:

0.00000660

AC:

AN:

151630

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74006

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000196

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.052

BayesDel_noAF

Benign

-0.31

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0071

T;.;T;.;.

Eigen

Uncertain

0.41

Eigen_PC

Uncertain

0.40

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.85

D;T;D;.;D

M_CAP

Benign

0.020

MetaRNN

Benign

0.21

T;T;T;T;T

MetaSVM

Benign

-0.77

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-2.1

N;N;.;D;D

REVEL

Benign

0.14

Sift

Uncertain

0.0080

D;D;.;D;D

Sift4G

Benign

0.28

T;D;T;T;T

Polyphen

0.97

D;D;.;.;.

Vest4

0.30

MutPred

0.19

Loss of ubiquitination at K267 (P = 8e-04);.;.;.;.;

MVP

0.74

MPC

0.50

ClinPred

0.93

GERP RS

4.3

Varity_R

0.12

gMVP

0.11

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over