dbSNP rs115988985: CEP83:p.Ala146Val (chr12-94400962-G-A) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

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

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.41

Variant links:

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]

CEP83 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 21 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEP83	NM_016122.3 link	c.437C>T	p.Ala146Val	missense_variant	Exon 6 of 17	ENST00000397809.10	NP_057206.2	Q9Y592-1Q3B787

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CEP83	ENST00000397809.10 link	c.437C>T	p.Ala146Val	missense_variant	Exon 6 of 17	1	NM_016122.3	ENSP00000380911.4		Q9Y592-1

Frequencies

GnomAD3 genomes

AF:

0.00923

AC:

1404

AN:

152130

Hom.:

Cov.:

show subpopulations

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.:

AF XY:

0.00159

AC XY:

152

AN XY:

95776

show subpopulations

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.:

Cov.:

AF XY:

0.000730

AC XY:

458

AN XY:

627232

show subpopulations

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.:

Cov.:

AF XY:

0.00908

AC XY:

676

AN XY:

74456

show subpopulations

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.:

Bravo

AF:

0.0108

ESP6500AA

AF:

0.0327

AC:

118

ESP6500EA

AF:

0.000123

AC:

ExAC

AF:

0.00278

AC:

335

Asia WGS

AF:

0.000290

AC:

AN:

3460

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Nephronophthisis 18

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.36

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.038

.;.;T;T

Eigen

Benign

0.17

Eigen_PC

Uncertain

0.31

FATHMM_MKL

Uncertain

0.90

LIST_S2

Uncertain

0.92

.;D;D;D

MetaRNN

Benign

0.0038

T;T;T;T

MetaSVM

Benign

-0.94

PrimateAI

Benign

0.29

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

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over