8-93726401-G-A

Variant names:

• chr8-93726401-G-A
• rs36117362
• NM_145269.5:c.665G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_145269.5(CIBAR1):​c.665G>A​(p.Arg222Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.11 in 1,610,312 control chromosomes in the GnomAD database, including 10,792 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.096 (838 hom., cov: 32)
  • Exomes 𝑓: 0.11 (9954 hom.)
• Consequence: CIBAR1 NM_145269.5 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 7.63

Genes affected

CIBAR1 (HGNC:30452): (CBY1 interacting BAR domain containing 1) Enables phospholipid binding activity. Involved in several processes, including inner mitochondrial membrane organization; limb morphogenesis; and membrane tubulation. Located in several cellular components, including centriole; ciliary base; and mitochondrial crista. [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=0.0024147034).
• BP6: Variant 8-93726401-G-A is Benign according to our data. Variant chr8-93726401-G-A is described in ClinVar as [Benign]. Clinvar id is 3056249.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.12 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CIBAR1	NM_145269.5	c.665G>A	p.Arg222Gln	missense_variant	Exon 8 of 9	ENST00000518322.6	NP_660312.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CIBAR1	ENST00000518322.6	c.665G>A	p.Arg222Gln	missense_variant	Exon 8 of 9	5	NM_145269.5	ENSP00000429367.1

Frequencies

GnomAD3 genomes AF: 0.0962 AC: 14618 AN: 151900 Hom.: 838 Cov.: 32

Gnomad AFR AF: 0.0596

Gnomad AMI AF: 0.188

Gnomad AMR AF: 0.0880

Gnomad ASJ AF: 0.140

Gnomad EAS AF: 0.00115

Gnomad SAS AF: 0.0624

Gnomad FIN AF: 0.121

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.122

Gnomad OTH AF: 0.117

GnomAD2 exomes AF: 0.0960 AC: 23771 AN: 247656 AF XY: 0.0976

Gnomad AFR exome AF: 0.0546

Gnomad AMR exome AF: 0.0713

Gnomad ASJ exome AF: 0.137

Gnomad EAS exome AF: 0.000335

Gnomad FIN exome AF: 0.111

Gnomad NFE exome AF: 0.125

Gnomad OTH exome AF: 0.116

GnomAD4 exome AF: 0.111 AC: 162530 AN: 1458294 Hom.: 9954 Cov.: 30 AF XY: 0.111 AC XY: 80507 AN XY: 725530

Gnomad4 AFR exome AF: 0.0544 AC: 1818 AN: 33396

Gnomad4 AMR exome AF: 0.0760 AC: 3383 AN: 44506

Gnomad4 ASJ exome AF: 0.137 AC: 3561 AN: 26068

Gnomad4 EAS exome AF: 0.000353 AC: 14 AN: 39616

Gnomad4 SAS exome AF: 0.0666 AC: 5733 AN: 86060

Gnomad4 FIN exome AF: 0.110 AC: 5855 AN: 53308

Gnomad4 NFE exome AF: 0.122 AC: 135083 AN: 1109348

Gnomad4 Remaining exome AF: 0.107 AC: 6466 AN: 60234

GnomAD4 genome AF: 0.0961 AC: 14614 AN: 152018 Hom.: 838 Cov.: 32 AF XY: 0.0945 AC XY: 7020 AN XY: 74294

Gnomad4 AFR AF: 0.0595 AC: 0.0595049 AN: 0.0595049

Gnomad4 AMR AF: 0.0879 AC: 0.0879272 AN: 0.0879272

Gnomad4 ASJ AF: 0.140 AC: 0.139562 AN: 0.139562

Gnomad4 EAS AF: 0.00116 AC: 0.00115652 AN: 0.00115652

Gnomad4 SAS AF: 0.0623 AC: 0.0622924 AN: 0.0622924

Gnomad4 FIN AF: 0.121 AC: 0.120709 AN: 0.120709

Gnomad4 NFE AF: 0.122 AC: 0.121951 AN: 0.121951

Gnomad4 OTH AF: 0.116 AC: 0.116224 AN: 0.116224

Alfa AF: 0.114 Hom.: 2648

Bravo AF: 0.0944

TwinsUK AF: 0.115 AC: 426

ALSPAC AF: 0.120 AC: 464

ESP6500AA AF: 0.0506 AC: 184

ESP6500EA AF: 0.124 AC: 1011

ExAC AF: 0.0961 AC: 11608

Asia WGS AF: 0.0260 AC: 91 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

CIBAR1-related disorder Benign:1

Oct 28, 2019

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	0.12
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.10
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.096	T;.;T;.;.;T
Eigen	Uncertain	0.37
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.89	D;T;D;.;D;D
MetaRNN	Benign	0.0024	T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-2.3	N;N;.;D;D;D
REVEL	Benign	0.24
Sift	Benign	0.17	T;T;.;T;T;T
Sift4G	Uncertain	0.021	D;T;D;T;T;D
Polyphen		0.33	B;B;.;.;.;.
Vest4		0.31
MPC		0.18
ClinPred		0.019	T
GERP RS		5.5
Varity_R		0.31
gMVP		0.57
Mutation Taster		=92/8	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.19		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: rs36117362; hg19: chr8-94738629; COSMIC: COSV108183185; COSMIC: COSV108183185;