18-13116433-G-T

Position:

• chr18-13116433-G-T

Variant summary

Our verdict is Benign. Variant got -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. 13/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• 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

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]

CEP192 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CEP192	NM_032142.4	c.7346G>T	p.Arg2449Leu	missense_variant	43/45	ENST00000506447.5	NP_115518.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CEP192	ENST00000506447.5	c.7346G>T	p.Arg2449Leu	missense_variant	43/45	5	NM_032142.4	ENSP00000427550.1

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

GnomAD3 exomes AF: 0.663 AC: 165110 AN: 248966 Hom.: 55931 AF XY: 0.660 AC XY: 88815 AN XY: 134488

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 SAS exome AF: 0.686

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

Gnomad4 AFR exome AF: 0.943

Gnomad4 AMR exome AF: 0.617

Gnomad4 ASJ exome AF: 0.737

Gnomad4 EAS exome AF: 0.838

Gnomad4 SAS exome AF: 0.688

Gnomad4 FIN exome AF: 0.601

Gnomad4 NFE exome AF: 0.608

Gnomad4 OTH exome AF: 0.668

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

Gnomad4 AFR AF: 0.928

Gnomad4 AMR AF: 0.677

Gnomad4 ASJ AF: 0.730

Gnomad4 EAS AF: 0.803

Gnomad4 SAS AF: 0.704

Gnomad4 FIN AF: 0.611

Gnomad4 NFE AF: 0.609

Gnomad4 OTH AF: 0.720

Alfa AF: 0.642 Hom.: 76305

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 v4.3

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;T
MetaRNN	Benign	6.0e-7	T;T
MetaSVM	Benign	-1.0	T
PrimateAI	Benign	0.41	T
PROVEAN	Benign	1.7	N;.
REVEL	Benign	0.10
Sift	Benign	1.0	T;.
Sift4G	Benign	1.0	T;T
Vest4		0.16
MPC		0.12
ClinPred		0.022	T
GERP RS		4.8
Varity_R		0.067
gMVP		0.25

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

Publications

LitVar

Other links and lift over

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