Genetic Variant CIBAR2:p.Val256Phe (chr16-85099334-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_198491.3(CIBAR2):c.766G>T(p.Val256Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000706 in 1,415,570 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: not found (cov: 32)

Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

CIBAR2
NM_198491.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.463

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]

CIBAR2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07275987).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CIBAR2	NM_198491.3 link	c.766G>T	p.Val256Phe	missense_variant	Exon 9 of 9	ENST00000539556.6	NP_940893.1	Q6ZTR7A0A1X7SC74
CIBAR2	XM_011523063.2 link	c.766G>T	p.Val256Phe	missense_variant	Exon 9 of 10		XP_011521365.1	Q6ZTR7A0A1X7SC74
CIBAR2	XM_017023198.2 link	c.766G>T	p.Val256Phe	missense_variant	Exon 9 of 10		XP_016878687.1
CIBAR2	NM_001366920.1 link	c.754-653G>T		intron_variant	Intron 8 of 8		NP_001353849.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CIBAR2	ENST00000539556.6 link	c.766G>T	p.Val256Phe	missense_variant	Exon 9 of 9	5	NM_198491.3	ENSP00000443411.1		A0A1X7SC74
CIBAR2	ENST00000618669.3 link	c.469-653G>T		intron_variant	Intron 6 of 6	5		ENSP00000478373.1		A0A087WU51

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.06e-7

AC:

AN:

1415570

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

706986

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32508

American (AMR)

AF:

0.00

AC:

AN:

44664

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25848

East Asian (EAS)

AF:

0.00

AC:

AN:

39478

South Asian (SAS)

AF:

0.00

AC:

AN:

85360

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53400

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5686

European-Non Finnish (NFE)

AF:

9.35e-7

AC:

AN:

1069854

Other (OTH)

AF:

0.00

AC:

AN:

58772

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jun 06, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.766G>T (p.V256F) alteration is located in exon 9 (coding exon 9) of the FAM92B gene. This alteration results from a G to T substitution at nucleotide position 766, causing the valine (V) at amino acid position 256 to be replaced by a phenylalanine (F). 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

0.084

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.63

CADD

Benign

4.4

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.0033

.;T

Eigen

Benign

-0.81

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.015

LIST_S2

Benign

0.36

T;T

M_CAP

Benign

0.0018

MetaRNN

Benign

0.073

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.34

.;N

PhyloP100

-0.46

PrimateAI

Benign

0.31

PROVEAN

Benign

-1.2

N;.

REVEL

Benign

0.057

Sift

Benign

0.29

T;.

Sift4G

Benign

0.11

T;T

Polyphen

0.94

.;P

Vest4

0.089

MutPred

0.23

Gain of catalytic residue at V256 (P = 0.0285);Gain of catalytic residue at V256 (P = 0.0285);

MVP

0.13

MPC

0.068

ClinPred

0.30

GERP RS

-1.3

Varity_R

0.052

gMVP

0.050

Mutation Taster

=97/3

polymorphism

(source)

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

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16-85099334-C-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over