rs375222323

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr16-85102326-T-C
• chr16-85102326-T-G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_198491.3(CIBAR2):​c.539A>G​(p.Lys180Arg) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000507 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. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000051 (0 hom.)
• Consequence: CIBAR2 NM_198491.3 missense, splice_region
• Scores: Splicing: ADA: 0.00007271
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.228
• Publications: 1 publications found

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

Our verdict: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.052315116).
• BP6: Variant 16-85102326-T-C is Benign according to our data. Variant chr16-85102326-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 3144950.Status of the report is criteria_provided_single_submitter, 1 stars.

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>G	p.Lys180Arg	missense splice_region	Exon 7 of 9	NP_940893.1	A0A1X7SC74
	CIBAR2	NM_001366920.1		c.539A>G	p.Lys180Arg	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>G	p.Lys180Arg	missense splice_region	Exon 7 of 9	ENSP00000443411.1	A0A1X7SC74
	CIBAR2	ENST00000618669.3	TSL:5	c.254A>G	p.Lys85Arg	missense splice_region	Exon 5 of 7	ENSP00000478373.1	A0A087WU51

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000119 AC: 3 AN: 251128 AF XY: 0.00000736

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000264

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000507 AC: 73 AN: 1439142 Hom.: 0 Cov.: 26 AF XY: 0.0000460 AC XY: 33 AN XY: 717510

African (AFR) AF: 0.00 AC: 0 AN: 32986

American (AMR) AF: 0.00 AC: 0 AN: 44682

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25968

East Asian (EAS) AF: 0.00 AC: 0 AN: 39570

South Asian (SAS) AF: 0.00 AC: 0 AN: 85798

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53328

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5724

European-Non Finnish (NFE) AF: 0.0000669 AC: 73 AN: 1091496

Other (OTH) AF: 0.00 AC: 0 AN: 59590

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000331 Hom.: 0

Bravo AF: 0.00000756

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00000824 AC: 1

EpiCase AF: 0.0000545

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	0.93
DANN	Benign	0.63
DEOGEN2	Benign	0.0037	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.094	N
LIST_S2	Benign	0.38	T
M_CAP	Benign	0.0087	T
MetaRNN	Benign	0.052	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.78	N
PhyloP100		0.23
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.66	N
REVEL	Benign	0.042
Sift	Benign	0.31	T
Sift4G	Benign	0.18	T
Polyphen		0.0090	B
Vest4		0.17
MVP		0.17
MPC		0.032
ClinPred		0.076	T
GERP RS		-1.8
Varity_R		0.031
gMVP		0.064
Mutation Taster		=89/11	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000073
dbscSNV1_RF	Benign	0.068
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs375222323; hg19: chr16-85135932;