16-85102326-T-G

Variant names:

• chr16-85102326-T-G
• rs375222323
• NM_198491.3:c.539A>C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_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. 18/23 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.

• 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

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=0.051067293).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CIBAR2	NM_198491.3	c.539A>C	p.Lys180Thr	missense_variant, splice_region_variant	Exon 7 of 9	ENST00000539556.6	NP_940893.1
CIBAR2	NM_001366920.1	c.539A>C	p.Lys180Thr	missense_variant, splice_region_variant	Exon 7 of 9		NP_001353849.1
CIBAR2	XM_011523063.2	c.539A>C	p.Lys180Thr	missense_variant, splice_region_variant	Exon 7 of 10		XP_011521365.1
CIBAR2	XM_017023198.2	c.539A>C	p.Lys180Thr	missense_variant, splice_region_variant	Exon 7 of 10		XP_016878687.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CIBAR2	ENST00000539556.6	c.539A>C	p.Lys180Thr	missense_variant, splice_region_variant	Exon 7 of 9	5	NM_198491.3	ENSP00000443411.1
CIBAR2	ENST00000618669.3	c.254A>C	p.Lys85Thr	missense_variant, splice_region_variant	Exon 5 of 7	5		ENSP00000478373.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000556 AC: 8 AN: 1439142 Hom.: 0 Cov.: 26 AF XY: 0.00000418 AC XY: 3 AN XY: 717510

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: 0.00000733

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	2.8
DANN	Benign	0.58
DEOGEN2	Benign	0.0029	.;T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.22	N
LIST_S2	Benign	0.39	T;T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.051	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	.;L
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-0.22	N;.
REVEL	Benign	0.040
Sift	Benign	0.71	T;.
Sift4G	Benign	0.52	T;T
Polyphen		0.016	.;B
Vest4		0.31
MutPred		0.40		Loss of methylation at K180 (P = 0.002);Loss of methylation at K180 (P = 0.002);
MVP		0.085
MPC		0.040
ClinPred		0.070	T
GERP RS		-1.8
Varity_R		0.044
gMVP		0.15

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

LitVar

Other links and lift over

dbSNP: rs375222323; hg19: chr16-85135932;