rs148769208

chr12-94403179-A-G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_016122.3(CEP83):c.408T>C(p.Asn136=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0107 in 1,523,042 control chromosomes in the GnomAD database, including 130 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0073 (6 hom., cov: 32)
  • Exomes 𝑓: 0.011 (124 hom.)
• Consequence: CEP83 NM_016122.3 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.343

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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP6: Variant 12-94403179-A-G is Benign according to our data. Variant chr12-94403179-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 474964.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.343 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00733 (1116/152314) while in subpopulation NFE AF= 0.0114 (777/68028). AF 95% confidence interval is 0.0108. There are 6 homozygotes in gnomad4. There are 514 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CEP83	NM_016122.3	c.408T>C	p.Asn136=	synonymous_variant	5/17	ENST00000397809.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CEP83	ENST00000397809.10	c.408T>C	p.Asn136=	synonymous_variant	5/17	1	NM_016122.3	P1

Frequencies

GnomAD3 genomes AF: 0.00733 AC: 1116 AN: 152196 Hom.: 6 Cov.: 32

Gnomad AFR AF: 0.00210

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.00759

Gnomad ASJ AF: 0.00835

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00828

Gnomad FIN AF: 0.00340

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0114

Gnomad OTH AF: 0.0115

GnomAD3 exomes AF: 0.00869 AC: 2131 AN: 245242 Hom.: 12 AF XY: 0.00920 AC XY: 1223 AN XY: 133000

Gnomad AFR exome AF: 0.00156

Gnomad AMR exome AF: 0.00483

Gnomad ASJ exome AF: 0.0104

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0101

Gnomad FIN exome AF: 0.00341

Gnomad NFE exome AF: 0.0126

Gnomad OTH exome AF: 0.0103

GnomAD4 exome AF: 0.0110 AC: 15109 AN: 1370728 Hom.: 124 Cov.: 22 AF XY: 0.0111 AC XY: 7623 AN XY: 687330

Gnomad4 AFR exome AF: 0.00191

Gnomad4 AMR exome AF: 0.00521

Gnomad4 ASJ exome AF: 0.0112

Gnomad4 EAS exome AF: 0.0000256

Gnomad4 SAS exome AF: 0.00964

Gnomad4 FIN exome AF: 0.00363

Gnomad4 NFE exome AF: 0.0125

Gnomad4 OTH exome AF: 0.00986

GnomAD4 genome AF: 0.00733 AC: 1116 AN: 152314 Hom.: 6 Cov.: 32 AF XY: 0.00690 AC XY: 514 AN XY: 74476

Gnomad4 AFR AF: 0.00209

Gnomad4 AMR AF: 0.00758

Gnomad4 ASJ AF: 0.00835

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00849

Gnomad4 FIN AF: 0.00340

Gnomad4 NFE AF: 0.0114

Gnomad4 OTH AF: 0.0114

Alfa AF: 0.0104 Hom.: 5

Bravo AF: 0.00801

Asia WGS AF: 0.00173 AC: 6 AN: 3478

EpiCase AF: 0.0131

EpiControl AF: 0.0135

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	May 04, 2021	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jul 01, 2023	CEP83: BP4, BS1, BS2 -

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
BayesDel_noAF	Benign	-0.55
Cadd	Benign	3.3
Dann	Benign	0.49
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs148769208; hg19: chr12-94796955; COSMIC: COSV100353417; COSMIC: COSV100353417;