16-85099195-T-C

Variant summary

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

The NM_198491.3(CIBAR2):​c.905A>G​(p.His302Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000038 in 1,579,614 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 (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000035 ( 0 hom. )

Consequence

CIBAR2
NM_198491.3 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.289

Publications

1 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=0.028528959).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CIBAR2NM_198491.3 linkc.905A>G p.His302Arg missense_variant Exon 9 of 9 ENST00000539556.6 NP_940893.1 Q6ZTR7A0A1X7SC74
CIBAR2XM_011523063.2 linkc.905A>G p.His302Arg missense_variant Exon 9 of 10 XP_011521365.1 Q6ZTR7A0A1X7SC74
CIBAR2NM_001366920.1 linkc.754-514A>G intron_variant Intron 8 of 8 NP_001353849.1
CIBAR2XM_017023198.2 linkc.832+73A>G intron_variant Intron 9 of 9 XP_016878687.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CIBAR2ENST00000539556.6 linkc.905A>G p.His302Arg missense_variant Exon 9 of 9 5 NM_198491.3 ENSP00000443411.1 A0A1X7SC74
CIBAR2ENST00000618669.3 linkc.469-514A>G intron_variant Intron 6 of 6 5 ENSP00000478373.1 A0A087WU51

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152130
Hom.:
0
Cov.:
32
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:
0.000193
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
GnomAD2 exomes
AF:
0.0000447
AC:
10
AN:
223822
AF XY:
0.0000248
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000529
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000967
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000350
AC:
5
AN:
1427484
Hom.:
0
Cov.:
30
AF XY:
0.00000283
AC XY:
2
AN XY:
707918
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
31934
American (AMR)
AF:
0.00
AC:
0
AN:
38416
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
23880
East Asian (EAS)
AF:
0.000103
AC:
4
AN:
38648
South Asian (SAS)
AF:
0.00
AC:
0
AN:
81320
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
52456
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5584
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1096378
Other (OTH)
AF:
0.0000170
AC:
1
AN:
58868
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.505
Heterozygous variant carriers
0
1
1
2
2
3
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:
0.00000657
AC:
1
AN:
152130
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74316
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
41416
American (AMR)
AF:
0.00
AC:
0
AN:
15282
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3470
East Asian (EAS)
AF:
0.000193
AC:
1
AN:
5186
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4832
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10610
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
68016
Other (OTH)
AF:
0.00
AC:
0
AN:
2090
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.525
Heterozygous variant carriers
0
0
1
1
2
2
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:
0.00000378
ExAC
AF:
0.0000165
AC:
2

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Apr 07, 2023
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

The c.905A>G (p.H302R) alteration is located in exon 9 (coding exon 9) of the FAM92B gene. This alteration results from a A to G substitution at nucleotide position 905, causing the histidine (H) at amino acid position 302 to be replaced by an arginine (R). 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
0.065
BayesDel_addAF
Benign
-0.58
T
BayesDel_noAF
Benign
-0.73
CADD
Benign
0.30
DANN
Benign
0.42
DEOGEN2
Benign
0.0012
.;T
Eigen
Benign
-1.4
Eigen_PC
Benign
-1.5
FATHMM_MKL
Benign
0.012
N
LIST_S2
Benign
0.34
T;T
M_CAP
Benign
0.0012
T
MetaRNN
Benign
0.029
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.0
.;N
PhyloP100
0.29
PrimateAI
Benign
0.36
T
PROVEAN
Benign
-0.060
N;.
REVEL
Benign
0.021
Sift
Benign
0.10
T;.
Sift4G
Pathogenic
0.0
D;D
Polyphen
0.063
.;B
Vest4
0.031
MutPred
0.13
Loss of catalytic residue at H302 (P = 0.0501);Loss of catalytic residue at H302 (P = 0.0501);
MVP
0.072
MPC
0.040
ClinPred
0.031
T
GERP RS
-0.11
Varity_R
0.031
gMVP
0.030
Mutation Taster
=99/1
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: rs767350357; hg19: chr16-85132801; API