18-13116433-G-T

Variant names:

• chr18-13116433-G-T
• rs1786263
• NM_032142.4:c.7346G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032142.4(CEP192):​c.7346G>T​(p.Arg2449Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.64 in 1,610,386 control chromosomes in the GnomAD database, including 335,822 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.72 (40660 hom., cov: 31)
  • Exomes 𝑓: 0.63 (295162 hom.)
• Consequence: CEP192 NM_032142.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.555
• Publications: 61 publications found

Genes affected

CEP192 (HGNC:25515): (centrosomal protein 192) Enables phosphatase binding activity. Involved in centrosome-templated microtubule nucleation; mitotic spindle assembly; and protein localization to centrosome. Located in centriole; centrosome; and cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=5.9512035E-7).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.92 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032142.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP192	NM_032142.4	MANE Select	c.7346G>T	p.Arg2449Leu	missense	Exon 43 of 45	NP_115518.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP192	ENST00000506447.5	TSL:5 MANE Select	c.7346G>T	p.Arg2449Leu	missense	Exon 43 of 45	ENSP00000427550.1
	CEP192	ENST00000511820.6	TSL:1	c.5960G>T	p.Arg1987Leu	missense	Exon 33 of 35	ENSP00000467038.1
	CEP192	ENST00000510237.5	TSL:1	n.*204G>T		non_coding_transcript_exon	Exon 33 of 35	ENSP00000423147.1

Frequencies

GnomAD3 genomes AF: 0.717 AC: 108982 AN: 151916 Hom.: 40598 Cov.: 31

Gnomad AFR AF: 0.928

Gnomad AMI AF: 0.644

Gnomad AMR AF: 0.678

Gnomad ASJ AF: 0.730

Gnomad EAS AF: 0.803

Gnomad SAS AF: 0.704

Gnomad FIN AF: 0.611

Gnomad MID AF: 0.769

Gnomad NFE AF: 0.609

Gnomad OTH AF: 0.716

GnomAD2 exomes AF: 0.663 AC: 165110 AN: 248966 AF XY: 0.660

Gnomad AFR exome AF: 0.936

Gnomad AMR exome AF: 0.610

Gnomad ASJ exome AF: 0.744

Gnomad EAS exome AF: 0.788

Gnomad FIN exome AF: 0.609

Gnomad NFE exome AF: 0.618

Gnomad OTH exome AF: 0.644

GnomAD4 exome AF: 0.632 AC: 921131 AN: 1458352 Hom.: 295162 Cov.: 38 AF XY: 0.633 AC XY: 458815 AN XY: 725316

African (AFR) AF: 0.943 AC: 31416 AN: 33304

American (AMR) AF: 0.617 AC: 27229 AN: 44138

Ashkenazi Jewish (ASJ) AF: 0.737 AC: 19230 AN: 26098

East Asian (EAS) AF: 0.838 AC: 33218 AN: 39618

South Asian (SAS) AF: 0.688 AC: 58786 AN: 85466

European-Finnish (FIN) AF: 0.601 AC: 32099 AN: 53394

Middle Eastern (MID) AF: 0.737 AC: 4241 AN: 5758

European-Non Finnish (NFE) AF: 0.608 AC: 674660 AN: 1110330

Other (OTH) AF: 0.668 AC: 40252 AN: 60246

GnomAD4 genome AF: 0.718 AC: 109097 AN: 152034 Hom.: 40660 Cov.: 31 AF XY: 0.717 AC XY: 53292 AN XY: 74296

African (AFR) AF: 0.928 AC: 38536 AN: 41520

American (AMR) AF: 0.677 AC: 10359 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.730 AC: 2534 AN: 3470

East Asian (EAS) AF: 0.803 AC: 4146 AN: 5160

South Asian (SAS) AF: 0.704 AC: 3389 AN: 4814

European-Finnish (FIN) AF: 0.611 AC: 6427 AN: 10512

Middle Eastern (MID) AF: 0.759 AC: 223 AN: 294

European-Non Finnish (NFE) AF: 0.609 AC: 41378 AN: 67948

Other (OTH) AF: 0.720 AC: 1519 AN: 2110

Alfa AF: 0.650 Hom.: 144139

Bravo AF: 0.733

TwinsUK AF: 0.607 AC: 2251

ALSPAC AF: 0.609 AC: 2348

ESP6500AA AF: 0.921 AC: 4056

ESP6500EA AF: 0.616 AC: 5297

ExAC AF: 0.671 AC: 81447

Asia WGS AF: 0.807 AC: 2803 AN: 3478

EpiCase AF: 0.630

EpiControl AF: 0.638

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.048
BayesDel_addAF	Benign	-0.72	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	7.5
DANN	Benign	0.41
DEOGEN2	Benign	0.0032	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-0.83
FATHMM_MKL	Benign	0.037	N
LIST_S2	Benign	0.063	T
MetaRNN	Benign	6.0e-7	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.56
PrimateAI	Benign	0.41	T
PROVEAN	Benign	1.7	N
REVEL	Benign	0.10
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Vest4		0.16
MPC		0.12
ClinPred		0.022	T
GERP RS		4.8
Varity_R		0.067
gMVP		0.25
Mutation Taster		=100/0	polymorphism (auto)

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: rs1786263; hg19: chr18-13116432; COSMIC: COSV58061635;