rs139046818

chr12-94335597-G-A

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BS1 BS2

The NM_016122.3(CEP83):c.1411C>T(p.Leu471=) variant causes a synonymous change. The variant allele was found at a frequency of 0.0176 in 1,562,332 control chromosomes in the GnomAD database, including 304 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. L471L) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.012 (22 hom., cov: 32)
  • Exomes 𝑓: 0.018 (282 hom.)
• Consequence: CEP83 NM_016122.3 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 3.66

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 -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.38).
• BP6: Variant 12-94335597-G-A is Benign according to our data. Variant chr12-94335597-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 474961.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0119 (1812/152000) while in subpopulation NFE AF= 0.0211 (1435/67934). AF 95% confidence interval is 0.0202. There are 22 homozygotes in gnomad4. There are 798 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 22 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CEP83	NM_016122.3	c.1411C>T	p.Leu471=	synonymous_variant	12/17	ENST00000397809.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CEP83	ENST00000397809.10	c.1411C>T	p.Leu471=	synonymous_variant	12/17	1	NM_016122.3	P1
CEP83	ENST00000339839.9	c.1411C>T	p.Leu471=	synonymous_variant	11/16	1		P1
CEP83	ENST00000547232.5	c.1312C>T	p.Leu438=	synonymous_variant, NMD_transcript_variant	12/17	1
CEP83	ENST00000546587.1	n.252C>T		non_coding_transcript_exon_variant	1/3	3

Frequencies

GnomAD3 genomes AF: 0.0119 AC: 1812 AN: 151882 Hom.: 22 Cov.: 32

Gnomad AFR AF: 0.00358

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.00669

Gnomad ASJ AF: 0.00403

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0112

Gnomad FIN AF: 0.00285

Gnomad MID AF: 0.00321

Gnomad NFE AF: 0.0211

Gnomad OTH AF: 0.0105

GnomAD3 exomes AF: 0.0116 AC: 2533 AN: 218410 Hom.: 29 AF XY: 0.0119 AC XY: 1413 AN XY: 118438

Gnomad AFR exome AF: 0.00281

Gnomad AMR exome AF: 0.00487

Gnomad ASJ exome AF: 0.00532

Gnomad EAS exome AF: 0.000188

Gnomad SAS exome AF: 0.00995

Gnomad FIN exome AF: 0.00281

Gnomad NFE exome AF: 0.0198

Gnomad OTH exome AF: 0.00937

GnomAD4 exome AF: 0.0182 AC: 25618 AN: 1410332 Hom.: 282 Cov.: 26 AF XY: 0.0178 AC XY: 12532 AN XY: 702078

Gnomad4 AFR exome AF: 0.00312

Gnomad4 AMR exome AF: 0.00485

Gnomad4 ASJ exome AF: 0.00519

Gnomad4 EAS exome AF: 0.000444

Gnomad4 SAS exome AF: 0.00909

Gnomad4 FIN exome AF: 0.00349

Gnomad4 NFE exome AF: 0.0218

Gnomad4 OTH exome AF: 0.0138

GnomAD4 genome AF: 0.0119 AC: 1812 AN: 152000 Hom.: 22 Cov.: 32 AF XY: 0.0107 AC XY: 798 AN XY: 74292

Gnomad4 AFR AF: 0.00357

Gnomad4 AMR AF: 0.00661

Gnomad4 ASJ AF: 0.00403

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0112

Gnomad4 FIN AF: 0.00285

Gnomad4 NFE AF: 0.0211

Gnomad4 OTH AF: 0.0104

Alfa AF: 0.0175 Hom.: 15

Bravo AF: 0.0119

Asia WGS AF: 0.00577 AC: 20 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 16, 2021

- -

Nephronophthisis 18 Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
Cadd	Benign	9.7
Dann	Benign	0.74

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: rs139046818; hg19: chr12-94729373; COSMIC: COSV100353332; COSMIC: COSV100353332;