rs115988985

chr12-94400962-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_016122.3(CEP83):c.437C>T(p.Ala146Val) variant causes a missense change. The variant allele was found at a frequency of 0.00175 in 1,425,758 control chromosomes in the GnomAD database, including 45 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0092 (21 hom., cov: 33)
  • Exomes 𝑓: 0.00086 (24 hom.)
• Consequence: CEP83 NM_016122.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.41

Genes affected

CEP83 (HGNC:17966): (centrosomal protein 83) The protein encoded by this gene is a centriolar protein involved in primary cilium assembly. Defects in this gene have been associated with infantile nephronophthisis and intellectual disability. [provided by RefSeq, Oct 2016]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.003816247).
• BP6: Variant 12-94400962-G-A is Benign according to our data. Variant chr12-94400962-G-A is described in ClinVar as [Benign]. Clinvar id is 474965.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00925 (1408/152248) while in subpopulation AFR AF= 0.0325 (1352/41552). AF 95% confidence interval is 0.0311. There are 21 homozygotes in gnomad4. There are 676 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 21 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CEP83	NM_016122.3	c.437C>T	p.Ala146Val	missense_variant	6/17	ENST00000397809.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CEP83	ENST00000397809.10	c.437C>T	p.Ala146Val	missense_variant	6/17	1	NM_016122.3	P1

Frequencies

GnomAD3 genomes AF: 0.00923 AC: 1404 AN: 152130 Hom.: 21 Cov.: 33

Gnomad AFR AF: 0.0325

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00288

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: 0.0000735

Gnomad OTH AF: 0.00335

GnomAD3 exomes AF: 0.00222 AC: 384 AN: 172588 Hom.: 9 AF XY: 0.00159 AC XY: 152 AN XY: 95776

Gnomad AFR exome AF: 0.0341

Gnomad AMR exome AF: 0.00126

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000106

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000114

Gnomad OTH exome AF: 0.00113

GnomAD4 exome AF: 0.000855 AC: 1089 AN: 1273510 Hom.: 24 Cov.: 24 AF XY: 0.000730 AC XY: 458 AN XY: 627232

Gnomad4 AFR exome AF: 0.0350

Gnomad4 AMR exome AF: 0.00150

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000814

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000187

Gnomad4 OTH exome AF: 0.00153

GnomAD4 genome AF: 0.00925 AC: 1408 AN: 152248 Hom.: 21 Cov.: 33 AF XY: 0.00908 AC XY: 676 AN XY: 74456

Gnomad4 AFR AF: 0.0325

Gnomad4 AMR AF: 0.00288

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000735

Gnomad4 OTH AF: 0.00331

Alfa AF: 0.00188 Hom.: 5

Bravo AF: 0.0108

ESP6500AA AF: 0.0327 AC: 118

ESP6500EA AF: 0.000123 AC: 1

ExAC AF: 0.00278 AC: 335

Asia WGS AF: 0.000290 AC: 1 AN: 3460

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Nephronophthisis 18 Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.36
Cadd	Uncertain	24
Dann	Uncertain	1.0
Eigen	Benign	0.17
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Uncertain	0.90	D
MetaRNN	Benign	0.0038	T;T;T;T
MetaSVM	Benign	-0.94	T
MutationTaster	Benign	0.99	N;N;N;N
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-1.6	N;N;.;N
REVEL	Benign	0.052
Sift	Benign	0.14	T;T;.;T
Sift4G	Benign	0.26	T;T;T;T
Polyphen		0.33	.;.;.;B
Vest4		0.35
MVP		0.81
MPC		0.20
ClinPred		0.011	T
GERP RS		4.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.15
gMVP		0.14

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: rs115988985; hg19: chr12-94794738; COSMIC: COSV99045918; COSMIC: COSV99045918;