Genetic Variant CIBAR2:p.Ala153Ser (chr16-85105407-C-A) – 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.457G>T(p.Ala153Ser) 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 1,613,448 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. 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. A153T) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

CIBAR2
NM_198491.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.09

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:

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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=0.035057724).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CIBAR2	NM_198491.3 link	c.457G>T	p.Ala153Ser	missense_variant	Exon 6 of 9	ENST00000539556.6	NP_940893.1	Q6ZTR7A0A1X7SC74
CIBAR2	NM_001366920.1 link	c.457G>T	p.Ala153Ser	missense_variant	Exon 6 of 9		NP_001353849.1
CIBAR2	XM_011523063.2 link	c.457G>T	p.Ala153Ser	missense_variant	Exon 6 of 10		XP_011521365.1	Q6ZTR7A0A1X7SC74
CIBAR2	XM_017023198.2 link	c.457G>T	p.Ala153Ser	missense_variant	Exon 6 of 10		XP_016878687.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CIBAR2	ENST00000539556.6 link	c.457G>T	p.Ala153Ser	missense_variant	Exon 6 of 9	5	NM_198491.3	ENSP00000443411.1		A0A1X7SC74
CIBAR2	ENST00000618669.3 link	c.172G>T	p.Ala58Ser	missense_variant	Exon 4 of 7	5		ENSP00000478373.1		A0A087WU51

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000399

AC:

AN:

250432

AF XY:

0.00000738

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS 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:

0.00000479

AC:

AN:

1461258

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

726986

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33476

American (AMR)

AF:

0.0000447

AC:

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86240

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53044

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1111800

Other (OTH)

AF:

0.0000497

AC:

AN:

60384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.446

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152190

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74358

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41432

American (AMR)

AF:

0.000131

AC:

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5200

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68042

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000287

Hom.:

Bravo

AF:

0.0000264

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.094

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.65

CADD

Benign

2.2

(source)

DANN

Benign

0.56

DEOGEN2

Benign

0.0017

.;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-0.93

FATHMM_MKL

Benign

0.24

LIST_S2

Benign

0.67

T;T

M_CAP

Benign

0.0061

MetaRNN

Benign

0.035

T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-1.4

.;N

PhyloP100

1.1

PrimateAI

Benign

0.27

PROVEAN

Benign

1.2

N;.

REVEL

Benign

0.065

Sift

Benign

1.0

T;.

Sift4G

Benign

1.0

T;T

Polyphen

0.013

.;B

Vest4

0.079

MutPred

0.35

Gain of phosphorylation at A153 (P = 0.0172);Gain of phosphorylation at A153 (P = 0.0172);

MVP

0.18

MPC

0.035

ClinPred

0.044

GERP RS

2.9

Varity_R

0.029

gMVP

0.052

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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chr16-85105407-C-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over