16-85099318-G-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_198491.3(CIBAR2):​c.782C>A​(p.Ala261Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000999 in 1,601,890 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A261S) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 31)
Exomes 𝑓: 0.0000083 ( 0 hom. )

Consequence

CIBAR2
NM_198491.3 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.417

Publications

0 publications found
Variant links:
Genes affected
CIBAR2 (HGNC:24781): (CBY1 interacting BAR domain containing 2) Predicted to be involved in cilium assembly. Predicted to be located in centriole and cytoplasm. Predicted to be active in ciliary basal body and ciliary transition zone. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.019491166).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CIBAR2NM_198491.3 linkc.782C>A p.Ala261Glu missense_variant Exon 9 of 9 ENST00000539556.6 NP_940893.1 Q6ZTR7A0A1X7SC74
CIBAR2XM_011523063.2 linkc.782C>A p.Ala261Glu missense_variant Exon 9 of 10 XP_011521365.1 Q6ZTR7A0A1X7SC74
CIBAR2XM_017023198.2 linkc.782C>A p.Ala261Glu missense_variant Exon 9 of 10 XP_016878687.1
CIBAR2NM_001366920.1 linkc.754-637C>A intron_variant Intron 8 of 8 NP_001353849.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CIBAR2ENST00000539556.6 linkc.782C>A p.Ala261Glu missense_variant Exon 9 of 9 5 NM_198491.3 ENSP00000443411.1 A0A1X7SC74
CIBAR2ENST00000618669.3 linkc.469-637C>A intron_variant Intron 6 of 6 5 ENSP00000478373.1 A0A087WU51

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
152156
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
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:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD2 exomes
AF:
0.0000398
AC:
10
AN:
251034
AF XY:
0.0000295
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000260
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000882
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000828
AC:
12
AN:
1449616
Hom.:
0
Cov.:
27
AF XY:
0.00000693
AC XY:
5
AN XY:
721846
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33236
American (AMR)
AF:
0.000179
AC:
8
AN:
44708
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26080
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39666
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86002
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53408
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5744
European-Non Finnish (NFE)
AF:
0.00000273
AC:
3
AN:
1100808
Other (OTH)
AF:
0.0000167
AC:
1
AN:
59964
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.450
Heterozygous variant carriers
0
1
2
2
3
4
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.0000263
AC:
4
AN:
152274
Hom.:
0
Cov.:
31
AF XY:
0.0000403
AC XY:
3
AN XY:
74460
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
41562
American (AMR)
AF:
0.000131
AC:
2
AN:
15296
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3466
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5174
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4824
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10606
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
294
European-Non Finnish (NFE)
AF:
0.0000294
AC:
2
AN:
68026
Other (OTH)
AF:
0.00
AC:
0
AN:
2114
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.513
Heterozygous variant carriers
0
1
2
2
3
4
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.00
Hom.:
0
Bravo
AF:
0.0000189
ExAC
AF:
0.0000494
AC:
6

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
May 24, 2023
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

The c.782C>A (p.A261E) alteration is located in exon 9 (coding exon 9) of the FAM92B gene. This alteration results from a C to A substitution at nucleotide position 782, causing the alanine (A) at amino acid position 261 to be replaced by a glutamic acid (E). 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
Benign
0.083
BayesDel_addAF
Benign
-0.49
T
BayesDel_noAF
Benign
-0.65
CADD
Benign
0.65
DANN
Benign
0.58
DEOGEN2
Benign
0.00092
.;T
Eigen
Benign
-1.1
Eigen_PC
Benign
-1.3
FATHMM_MKL
Benign
0.020
N
LIST_S2
Benign
0.37
T;T
M_CAP
Benign
0.0013
T
MetaRNN
Benign
0.019
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
-1.1
.;N
PhyloP100
-0.42
PrimateAI
Benign
0.25
T
PROVEAN
Benign
0.88
N;.
REVEL
Benign
0.035
Sift
Benign
0.44
T;.
Sift4G
Benign
0.73
T;T
Polyphen
0.54
.;P
Vest4
0.096
MutPred
0.13
Gain of solvent accessibility (P = 0.0488);Gain of solvent accessibility (P = 0.0488);
MVP
0.061
MPC
0.039
ClinPred
0.058
T
GERP RS
-1.1
Varity_R
0.046
gMVP
0.051
Mutation Taster
=98/2
polymorphism

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

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

Publications

Other links and lift over

dbSNP: rs557088845; hg19: chr16-85132924; API