Genetic Variant CIBAR2:p.Lys180Thr (chr16-85102326-T-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

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

The NM_198491.3(CIBAR2):c.539A>C(p.Lys180Thr) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000556 in 1,439,142 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 19/24 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. K180R) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000056 ( 0 hom. )

Consequence

CIBAR2
NM_198491.3 missense, splice_region

Scores

Splicing: ADA: 0.00003033

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.228

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]

CIBAR2 links:

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=0.051067293).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198491.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CIBAR2	NM_198491.3	MANE Select	c.539A>C	p.Lys180Thr	missense splice_region	Exon 7 of 9	NP_940893.1	A0A1X7SC74
	CIBAR2	NM_001366920.1		c.539A>C	p.Lys180Thr	missense splice_region	Exon 7 of 9	NP_001353849.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CIBAR2	ENST00000539556.6	TSL:5 MANE Select	c.539A>C	p.Lys180Thr	missense splice_region	Exon 7 of 9	ENSP00000443411.1	A0A1X7SC74
	CIBAR2	ENST00000618669.3	TSL:5	c.254A>C	p.Lys85Thr	missense splice_region	Exon 5 of 7	ENSP00000478373.1	A0A087WU51

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000556

AC:

AN:

1439142

Hom.:

Cov.:

AF XY:

0.00000418

AC XY:

AN XY:

717510

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32986

American (AMR)

AF:

0.00

AC:

AN:

44682

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25968

East Asian (EAS)

AF:

0.00

AC:

AN:

39570

South Asian (SAS)

AF:

0.00

AC:

AN:

85798

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53328

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5724

European-Non Finnish (NFE)

AF:

0.00000733

AC:

AN:

1091496

Other (OTH)

AF:

0.00

AC:

AN:

59590

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.54

CADD

Benign

2.8

(source)

DANN

Benign

0.58

DEOGEN2

Benign

0.0029

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.22

LIST_S2

Benign

0.39

M_CAP

Benign

0.011

MetaRNN

Benign

0.051

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

PhyloP100

0.23

PrimateAI

Benign

0.38

PROVEAN

Benign

-0.22

REVEL

Benign

0.040

Sift

Benign

0.71

Sift4G

Benign

0.52

Polyphen

0.016

Vest4

0.31

MutPred

0.40

Loss of methylation at K180 (P = 0.002)

MVP

0.085

MPC

0.040

ClinPred

0.070

GERP RS

-1.8

Varity_R

0.044

gMVP

0.15

Mutation Taster

=86/14

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000030

dbscSNV1_RF

Benign

0.0

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over