chr16-85107883-T-G

Variant names:

• chr16-85107883-T-G
• rs376548850
• NM_198491.3:c.389A>C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM1 PM2 BP4

The NM_198491.3(CIBAR2):​c.389A>C​(p.Lys130Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,834 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 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: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CIBAR2 NM_198491.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.562

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 Uncertain_significance. Variant got 3 ACMG points.

• PM1: In a mutagenesis_site Abolishes ability to induce membrane remodeling in the presence of CBY1; when associated with E-105; E-108; E-112; E-132 and E-134. (size 0) in uniprot entity CBAR2_HUMAN
• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.28692937).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CIBAR2	NM_198491.3	c.389A>C	p.Lys130Thr	missense_variant	Exon 4 of 9	ENST00000539556.6	NP_940893.1
CIBAR2	NM_001366920.1	c.389A>C	p.Lys130Thr	missense_variant	Exon 4 of 9		NP_001353849.1
CIBAR2	XM_011523063.2	c.389A>C	p.Lys130Thr	missense_variant	Exon 4 of 10		XP_011521365.1
CIBAR2	XM_017023198.2	c.389A>C	p.Lys130Thr	missense_variant	Exon 4 of 10		XP_016878687.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CIBAR2	ENST00000539556.6	c.389A>C	p.Lys130Thr	missense_variant	Exon 4 of 9	5	NM_198491.3	ENSP00000443411.1
CIBAR2	ENST00000618669.3	c.104A>C	p.Lys35Thr	missense_variant	Exon 2 of 7	5		ENSP00000478373.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251490 Hom.: 0 AF XY: 0.00000736 AC XY: 1 AN XY: 135920

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461834 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727224

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: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.079	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.077	.;T
Eigen	Uncertain	0.31
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Benign	0.69	D
LIST_S2	Benign	0.77	T;T
M_CAP	Benign	0.069	D
MetaRNN	Benign	0.29	T;T
MetaSVM	Benign	-0.56	T
MutationAssessor	Pathogenic	3.0	.;M
PrimateAI	Benign	0.38	T
PROVEAN	Pathogenic	-4.4	D;.
REVEL	Benign	0.24
Sift	Uncertain	0.0050	D;.
Sift4G	Uncertain	0.0060	D;D
Polyphen		0.93	.;P
Vest4		0.37
MutPred		0.48		Loss of ubiquitination at K130 (P = 0.0134);Loss of ubiquitination at K130 (P = 0.0134);
MVP		0.50
MPC		0.22
ClinPred		0.94	D
GERP RS		3.4
Varity_R		0.33
gMVP		0.31

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

LitVar

Other links and lift over

dbSNP: rs376548850; hg19: chr16-85141489;