rs189675715

Positions:

• chr12-94367934-G-A
• chr12-94367934-G-C

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.1203C>T​(p.Leu401=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000617 in 1,612,756 control chromosomes in the GnomAD database, including 4 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. L401L) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0023 (2 hom., cov: 32)
  • Exomes 𝑓: 0.00045 (2 hom.)
• Consequence: CEP83 NM_016122.3 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0860

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=-0.47).
• BP6: Variant 12-94367934-G-A is Benign according to our data. Variant chr12-94367934-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 541797.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.086 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00226 (343/152062) while in subpopulation AFR AF= 0.00752 (312/41476). AF 95% confidence interval is 0.00684. There are 2 homozygotes in gnomad4. There are 164 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CEP83	NM_016122.3	c.1203C>T	p.Leu401=	synonymous_variant	11/17	ENST00000397809.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CEP83	ENST00000397809.10	c.1203C>T	p.Leu401=	synonymous_variant	11/17	1	NM_016122.3	P1
CEP83	ENST00000339839.9	c.1203C>T	p.Leu401=	synonymous_variant	10/16	1		P1
CEP83	ENST00000547232.5	c.1104C>T	p.Leu368=	synonymous_variant, NMD_transcript_variant	11/17	1

Frequencies

GnomAD3 genomes AF: 0.00224 AC: 341 AN: 151944 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.00750

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000524

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000250

Gnomad OTH AF: 0.00240

GnomAD3 exomes AF: 0.000612 AC: 152 AN: 248496 Hom.: 0 AF XY: 0.000415 AC XY: 56 AN XY: 134798

Gnomad AFR exome AF: 0.00749

Gnomad AMR exome AF: 0.000204

Gnomad ASJ exome AF: 0.000498

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000987

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000186

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000446 AC: 652 AN: 1460694 Hom.: 2 Cov.: 30 AF XY: 0.000410 AC XY: 298 AN XY: 726628

Gnomad4 AFR exome AF: 0.00786

Gnomad4 AMR exome AF: 0.000314

Gnomad4 ASJ exome AF: 0.000383

Gnomad4 EAS exome AF: 0.000101

Gnomad4 SAS exome AF: 0.000116

Gnomad4 FIN exome AF: 0.0000188

Gnomad4 NFE exome AF: 0.000269

Gnomad4 OTH exome AF: 0.000812

GnomAD4 genome AF: 0.00226 AC: 343 AN: 152062 Hom.: 2 Cov.: 32 AF XY: 0.00221 AC XY: 164 AN XY: 74318

Gnomad4 AFR AF: 0.00752

Gnomad4 AMR AF: 0.000523

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000250

Gnomad4 OTH AF: 0.00238

Alfa AF: 0.00102 Hom.: 0

Bravo AF: 0.00267

EpiCase AF: 0.000218

EpiControl AF: 0.000119

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

CeGaT Center for Human Genetics Tuebingen

Jun 01, 2022

CEP83: BP4, BP7 -

Nephronophthisis 18 Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 24, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	6.7
DANN	Benign	0.69

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: rs189675715; hg19: chr12-94761710;