Variant 8-93726401-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_145269.5(CIBAR1):c.665G>A(p.Arg222Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.11 in 1,610,312 control chromosomes in the GnomAD database, including 10,792 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.096 ( 838 hom., cov: 32)

Exomes 𝑓: 0.11 ( 9954 hom. )

Consequence

CIBAR1
NM_145269.5 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 7.63

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0024147034).

BP6

Variant 8-93726401-G-A is Benign according to our data. Variant chr8-93726401-G-A is described in ClinVar as [Benign]. Clinvar id is 3056249.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.12 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CIBAR1	NM_145269.5 linkuse as main transcript	c.665G>A	p.Arg222Gln	missense_variant	8/9	ENST00000518322.6	NP_660312.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CIBAR1	ENST00000518322.6 linkuse as main transcript	c.665G>A	p.Arg222Gln	missense_variant	8/9	5	NM_145269.5	ENSP00000429367	P1	A1XBS5-1

Frequencies

GnomAD3 genomes

AF:

0.0962

AC:

14618

AN:

151900

Hom.:

838

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0596

Gnomad AMI

AF:

0.188

Gnomad AMR

AF:

0.0880

Gnomad ASJ

AF:

0.140

Gnomad EAS

AF:

0.00115

Gnomad SAS

AF:

0.0624

Gnomad FIN

AF:

0.121

Gnomad MID

AF:

0.123

Gnomad NFE

AF:

0.122

Gnomad OTH

AF:

0.117

GnomAD3 exomes

AF:

0.0960

AC:

23771

AN:

247656

Hom.:

1374

AF XY:

0.0976

AC XY:

13116

AN XY:

134372

show subpopulations

Gnomad AFR exome

AF:

0.0546

Gnomad AMR exome

AF:

0.0713

Gnomad ASJ exome

AF:

0.137

Gnomad EAS exome

AF:

0.000335

Gnomad SAS exome

AF:

0.0672

Gnomad FIN exome

AF:

0.111

Gnomad NFE exome

AF:

0.125

Gnomad OTH exome

AF:

0.116

GnomAD4 exome

AF:

0.111

AC:

162530

AN:

1458294

Hom.:

9954

Cov.:

AF XY:

0.111

AC XY:

80507

AN XY:

725530

show subpopulations

Gnomad4 AFR exome

AF:

0.0544

Gnomad4 AMR exome

AF:

0.0760

Gnomad4 ASJ exome

AF:

0.137

Gnomad4 EAS exome

AF:

0.000353

Gnomad4 SAS exome

AF:

0.0666

Gnomad4 FIN exome

AF:

0.110

Gnomad4 NFE exome

AF:

0.122

Gnomad4 OTH exome

AF:

0.107

GnomAD4 genome

AF:

0.0961

AC:

14614

AN:

152018

Hom.:

838

Cov.:

AF XY:

0.0945

AC XY:

7020

AN XY:

74294

show subpopulations

Gnomad4 AFR

AF:

0.0595

Gnomad4 AMR

AF:

0.0879

Gnomad4 ASJ

AF:

0.140

Gnomad4 EAS

AF:

0.00116

Gnomad4 SAS

AF:

0.0623

Gnomad4 FIN

AF:

0.121

Gnomad4 NFE

AF:

0.122

Gnomad4 OTH

AF:

0.116

Alfa

AF:

0.117

Hom.:

1935

Bravo

AF:

0.0944

TwinsUK

AF:

0.115

AC:

426

ALSPAC

AF:

0.120

AC:

464

ESP6500AA

AF:

0.0506

AC:

184

ESP6500EA

AF:

0.124

AC:

1011

ExAC

AF:

0.0961

AC:

11608

Asia WGS

AF:

0.0260

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

CIBAR1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 28, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.10

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.096

T;.;T;.;.;T

Eigen

Uncertain

0.37

Eigen_PC

Uncertain

0.50

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.89

D;T;D;.;D;D

MetaRNN

Benign

0.0024

T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationTaster

Benign

1.0

D;D;D;D;D

PrimateAI

Benign

0.40

PROVEAN

Benign

-2.3

N;N;.;D;D;D

REVEL

Benign

0.24

Sift

Benign

0.17

T;T;.;T;T;T

Sift4G

Uncertain

0.021

D;T;D;T;T;D

Polyphen

0.33

B;B;.;.;.;.

Vest4

0.31

MPC

0.18

ClinPred

0.019

GERP RS

5.5

Varity_R

0.31

gMVP

0.57

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.19

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over