16-85100179-G-C

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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. 14/20 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

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 Benign. Variant got -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 id 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 male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 15 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CIBAR2	NM_198491.3	c.713C>G	p.Thr238Ser	missense_variant	Exon 8 of 9	ENST00000539556.6	NP_940893.1
CIBAR2	NM_001366920.1	c.713C>G	p.Thr238Ser	missense_variant	Exon 8 of 9		NP_001353849.1
CIBAR2	XM_011523063.2	c.713C>G	p.Thr238Ser	missense_variant	Exon 8 of 10		XP_011521365.1
CIBAR2	XM_017023198.2	c.713C>G	p.Thr238Ser	missense_variant	Exon 8 of 10		XP_016878687.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CIBAR2	ENST00000539556.6	c.713C>G	p.Thr238Ser	missense_variant	Exon 8 of 9	5	NM_198491.3	ENSP00000443411.1
CIBAR2	ENST00000618669.3	c.428C>G	p.Thr143Ser	missense_variant	Exon 6 of 7	5		ENSP00000478373.1

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

GnomAD3 exomes AF: 0.00196 AC: 485 AN: 247458 Hom.: 7 AF XY: 0.00128 AC XY: 171 AN XY: 133848

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 SAS exome AF: 0.0000674

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

Gnomad4 AFR exome AF: 0.0295

Gnomad4 AMR exome AF: 0.00120

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000937

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000252

Gnomad4 OTH exome AF: 0.00172

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

Gnomad4 AFR AF: 0.0282

Gnomad4 AMR AF: 0.00209

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000588

Gnomad4 OTH AF: 0.00237

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

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

CIBAR2-related disorder Benign:1

Feb 01, 2021

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as 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	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;T
MetaRNN	Benign	0.0036	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.85	.;L
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.010	N;.
REVEL	Benign	0.020
Sift	Benign	0.40	T;.
Sift4G	Benign	0.37	T;T
Polyphen		0.15	.;B
Vest4		0.18
MutPred		0.25		Loss of relative solvent accessibility (P = 0.0071);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

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

Publications

LitVar

Other links and lift over

dbSNP: rs148969047; hg19: chr16-85133785;