rs148969047

Variant names:

• chr16-85100179-G-C
• rs148969047
• NM_198491.3:c.713C>G

Your query was ambiguous. Multiple possible variants found:

• chr16-85100179-G-C
• chr16-85100179-G-T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BS1 BS2

The NM_198491.3(CIBAR2):​c.713C>G​(p.Thr238Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00149 in 1,611,644 control chromosomes in the GnomAD database, including 29 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0080 (15 hom., cov: 31)
  • Exomes 𝑓: 0.00081 (14 hom.)
• Consequence: CIBAR2 NM_198491.3 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 1.15
• 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: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0036479533).
• BP6: Variant 16-85100179-G-C is Benign according to our data. Variant chr16-85100179-G-C is described in ClinVar as Benign. ClinVar VariationId is 3038426.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00797 (1213/152284) while in subpopulation AFR AF = 0.0282 (1172/41558). AF 95% confidence interval is 0.0269. There are 15 homozygotes in GnomAd4. There are 542 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 15 gene

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.713C>G	p.Thr238Ser	missense	Exon 8 of 9	NP_940893.1	A0A1X7SC74
	CIBAR2	NM_001366920.1		c.713C>G	p.Thr238Ser	missense	Exon 8 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.713C>G	p.Thr238Ser	missense	Exon 8 of 9	ENSP00000443411.1	A0A1X7SC74
	CIBAR2	ENST00000618669.3	TSL:5	c.428C>G	p.Thr143Ser	missense	Exon 6 of 7	ENSP00000478373.1	A0A087WU51

Frequencies

GnomAD3 genomes AF: 0.00796 AC: 1211 AN: 152166 Hom.: 15 Cov.: 31

Gnomad AFR AF: 0.0282

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00210

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: 0.0000588

Gnomad OTH AF: 0.00239

GnomAD2 exomes AF: 0.00196 AC: 485 AN: 247458 AF XY: 0.00128

Gnomad AFR exome AF: 0.0275

Gnomad AMR exome AF: 0.000935

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000443

Gnomad OTH exome AF: 0.000504

GnomAD4 exome AF: 0.000811 AC: 1184 AN: 1459360 Hom.: 14 Cov.: 31 AF XY: 0.000681 AC XY: 494 AN XY: 725756

African (AFR) AF: 0.0295 AC: 986 AN: 33452

American (AMR) AF: 0.00120 AC: 53 AN: 44140

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26120

East Asian (EAS) AF: 0.00 AC: 0 AN: 39670

South Asian (SAS) AF: 0.0000937 AC: 8 AN: 85344

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53396

Middle Eastern (MID) AF: 0.000868 AC: 5 AN: 5762

European-Non Finnish (NFE) AF: 0.0000252 AC: 28 AN: 1111150

Other (OTH) AF: 0.00172 AC: 104 AN: 60326

GnomAD4 genome AF: 0.00797 AC: 1213 AN: 152284 Hom.: 15 Cov.: 31 AF XY: 0.00728 AC XY: 542 AN XY: 74458

African (AFR) AF: 0.0282 AC: 1172 AN: 41558

American (AMR) AF: 0.00209 AC: 32 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68038

Other (OTH) AF: 0.00237 AC: 5 AN: 2110

Alfa AF: 0.000518 Hom.: 0

Bravo AF: 0.00895

ESP6500AA AF: 0.0312 AC: 137

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.00260 AC: 316

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.0000550

EpiControl AF: 0.0000597

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	CIBAR2-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.66	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	0.87
DANN	Benign	0.51
DEOGEN2	Benign	0.0034	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.084	N
LIST_S2	Benign	0.25	T
MetaRNN	Benign	0.0036	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.85	L
PhyloP100		1.2
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.010	N
REVEL	Benign	0.020
Sift	Benign	0.40	T
Sift4G	Benign	0.37	T
Polyphen		0.15	B
Vest4		0.18
MutPred		0.25		Loss of relative solvent accessibility (P = 0.0071)
MVP		0.14
MPC		0.034
ClinPred		0.0015	T
GERP RS		1.7
Varity_R		0.025
gMVP		0.057
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs148969047; hg19: chr16-85133785; COSMIC: COSV106116858;