NM_198491.3:c.782C>T

Variant names:

• chr16-85099318-G-A
• NM_198491.3:c.782C>T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_198491.3(CIBAR2):​c.782C>T​(p.Ala261Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000069 in 1,449,616 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: CIBAR2 NM_198491.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.417

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05051616).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CIBAR2	NM_198491.3	c.782C>T	p.Ala261Val	missense_variant	Exon 9 of 9	ENST00000539556.6	NP_940893.1
CIBAR2	XM_011523063.2	c.782C>T	p.Ala261Val	missense_variant	Exon 9 of 10		XP_011521365.1
CIBAR2	XM_017023198.2	c.782C>T	p.Ala261Val	missense_variant	Exon 9 of 10		XP_016878687.1
CIBAR2	NM_001366920.1	c.754-637C>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	c.782C>T	p.Ala261Val	missense_variant	Exon 9 of 9	5	NM_198491.3	ENSP00000443411.1
CIBAR2	ENST00000618669.3	c.469-637C>T		intron_variant	Intron 6 of 6	5		ENSP00000478373.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.90e-7 AC: 1 AN: 1449616 Hom.: 0 Cov.: 27 AF XY: 0.00000139 AC XY: 1 AN XY: 721846

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.08e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	5.5
DANN	Benign	0.68
DEOGEN2	Benign	0.0014	.;T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.010	N
LIST_S2	Benign	0.47	T;T
M_CAP	Benign	0.0011	T
MetaRNN	Benign	0.051	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	.;N
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-0.39	N;.
REVEL	Benign	0.014
Sift	Benign	0.55	T;.
Sift4G	Benign	0.24	T;T
Polyphen		0.083	.;B
Vest4		0.040
MutPred		0.11		Gain of sheet (P = 0.0827);Gain of sheet (P = 0.0827);
MVP		0.061
MPC		0.037
ClinPred		0.020	T
GERP RS		-1.1
Varity_R		0.022
gMVP		0.026

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-85132924;