Variant 8-93701253-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_145269.5(CIBAR1):c.56C>G(p.Ala19Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000682 in 1,613,394 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

CIBAR1
NM_145269.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.28

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 Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.32466638).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CIBAR1	NM_145269.5 link	c.56C>G	p.Ala19Gly	missense_variant	Exon 2 of 9	ENST00000518322.6	NP_660312.2	A1XBS5-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CIBAR1	ENST00000518322.6 link	c.56C>G	p.Ala19Gly	missense_variant	Exon 2 of 9	5	NM_145269.5	ENSP00000429367.1		A1XBS5-1

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000403

AC:

AN:

248158

Hom.:

AF XY:

0.00000743

AC XY:

AN XY:

134654

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000291

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000616

AC:

AN:

1461192

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

726824

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

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:

0.00000720

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152202

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jul 15, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.56C>G (p.A19G) alteration is located in exon 2 (coding exon 2) of the FAM92A1 gene. This alteration results from a C to G substitution at nucleotide position 56, causing the alanine (A) at amino acid position 19 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.48

BayesDel_addAF

Benign

-0.085

BayesDel_noAF

Benign

-0.28

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.016

T;.;T;.;T

Eigen

Uncertain

0.25

Eigen_PC

Uncertain

0.30

FATHMM_MKL

Uncertain

0.82

LIST_S2

Uncertain

0.94

D;D;D;D;D

M_CAP

Benign

0.024

MetaRNN

Benign

0.32

T;T;T;T;T

MetaSVM

Benign

-0.81

PrimateAI

Uncertain

0.63

PROVEAN

Benign

-1.9

N;N;N;N;.

REVEL

Benign

0.14

Sift

Benign

0.071

T;T;T;T;.

Sift4G

Benign

0.068

T;T;T;T;T

Polyphen

0.95

P;.;.;.;.

Vest4

0.52

MutPred

0.50

Gain of loop (P = 0.0121);Gain of loop (P = 0.0121);Gain of loop (P = 0.0121);Gain of loop (P = 0.0121);Gain of loop (P = 0.0121);

MVP

0.88

MPC

0.36

ClinPred

0.88

GERP RS

4.4

Varity_R

0.22

gMVP

0.48

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

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