chr16-85102232-G-C

Variant names:

• chr16-85102232-G-C
• rs61740642
• NM_198491.3:c.633C>G

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BP6 BS2

The NM_198491.3(CIBAR2):​c.633C>G​(p.Asp211Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00258 in 1,601,754 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0019 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0027 (9 hom.)
• Consequence: CIBAR2 NM_198491.3 missense
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 2.95
• Publications: 6 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 -9 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.041492373).
• BP6: Variant 16-85102232-G-C is Benign according to our data. Variant chr16-85102232-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 3040667.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS2: High Homozygotes in GnomAdExome4 at 9 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CIBAR2	NM_198491.3	c.633C>G	p.Asp211Glu	missense_variant	Exon 7 of 9	ENST00000539556.6	NP_940893.1
CIBAR2	NM_001366920.1	c.633C>G	p.Asp211Glu	missense_variant	Exon 7 of 9		NP_001353849.1
CIBAR2	XM_011523063.2	c.633C>G	p.Asp211Glu	missense_variant	Exon 7 of 10		XP_011521365.1
CIBAR2	XM_017023198.2	c.633C>G	p.Asp211Glu	missense_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.633C>G	p.Asp211Glu	missense_variant	Exon 7 of 9	5	NM_198491.3	ENSP00000443411.1
CIBAR2	ENST00000618669.3	c.348C>G	p.Asp116Glu	missense_variant	Exon 5 of 7	5		ENSP00000478373.1

Frequencies

GnomAD3 genomes AF: 0.00187 AC: 284 AN: 152148 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00268

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00320

Gnomad OTH AF: 0.00191

GnomAD2 exomes AF: 0.00165 AC: 416 AN: 251460 AF XY: 0.00166

Gnomad AFR exome AF: 0.000492

Gnomad AMR exome AF: 0.00139

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00308

Gnomad OTH exome AF: 0.00163

GnomAD4 exome AF: 0.00266 AC: 3853 AN: 1449488 Hom.: 9 Cov.: 28 AF XY: 0.00258 AC XY: 1860 AN XY: 722044

African (AFR) AF: 0.000482 AC: 16 AN: 33220

American (AMR) AF: 0.00123 AC: 55 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26076

East Asian (EAS) AF: 0.00 AC: 0 AN: 39630

South Asian (SAS) AF: 0.00 AC: 0 AN: 86014

European-Finnish (FIN) AF: 0.000112 AC: 6 AN: 53404

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5740

European-Non Finnish (NFE) AF: 0.00331 AC: 3646 AN: 1100710

Other (OTH) AF: 0.00217 AC: 130 AN: 59986

GnomAD4 genome AF: 0.00187 AC: 284 AN: 152266 Hom.: 0 Cov.: 32 AF XY: 0.00175 AC XY: 130 AN XY: 74450

African (AFR) AF: 0.000481 AC: 20 AN: 41542

American (AMR) AF: 0.00268 AC: 41 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

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

European-Non Finnish (NFE) AF: 0.00320 AC: 218 AN: 68026

Other (OTH) AF: 0.00189 AC: 4 AN: 2112

Alfa AF: 0.00253 Hom.: 1

Bravo AF: 0.00190

TwinsUK AF: 0.00431 AC: 16

ALSPAC AF: 0.00519 AC: 20

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00302 AC: 26

ExAC AF: 0.00159 AC: 193

EpiCase AF: 0.00338

EpiControl AF: 0.00344

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

CIBAR2-related disorder Benign:1

Feb 04, 2022

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.36
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.19	.;T
Eigen	Uncertain	0.33
Eigen_PC	Benign	0.16
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.66	T;T
M_CAP	Benign	0.044	D
MetaRNN	Benign	0.041	T;T
MetaSVM	Benign	-0.60	T
MutationAssessor	Pathogenic	3.1	.;M
PhyloP100		2.9
PrimateAI	Benign	0.40	T
PROVEAN	Uncertain	-3.2	D;.
REVEL	Uncertain	0.30
Sift	Uncertain	0.0030	D;.
Sift4G	Uncertain	0.0050	D;D
Polyphen		0.99	.;D
Vest4		0.68
MutPred		0.61		Loss of helix (P = 0.0558);Loss of helix (P = 0.0558);
MVP		0.37
MPC		0.18
ClinPred		0.060	T
GERP RS		3.8
Varity_R		0.25
gMVP		0.11
Mutation Taster		=96/4	polymorphism

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

Other links and lift over

dbSNP: rs61740642; hg19: chr16-85135838;