chr12-94308613-A-G

Position:

• chr12-94308613-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_016122.3(CEP83):​c.*200T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00432 in 368,770 control chromosomes in the GnomAD database, including 29 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0087 (25 hom., cov: 32)
  • Exomes 𝑓: 0.0012 (4 hom.)
• Consequence: CEP83 NM_016122.3 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.255

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 12-94308613-A-G is Benign according to our data. Variant chr12-94308613-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 1338909.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00868 (1322/152298) while in subpopulation AFR AF= 0.0304 (1265/41576). AF 95% confidence interval is 0.029. There are 25 homozygotes in gnomad4. There are 623 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 25 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CEP83	NM_016122.3	c.*200T>C		3_prime_UTR_variant	17/17	ENST00000397809.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CEP83	ENST00000397809.10	c.*200T>C		3_prime_UTR_variant	17/17	1	NM_016122.3	P1
CEP83	ENST00000339839.9	c.*200T>C		3_prime_UTR_variant	16/16	1		P1
CEP83	ENST00000552632.5	c.*30+170T>C		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.00867 AC: 1319 AN: 152180 Hom.: 26 Cov.: 32

Gnomad AFR AF: 0.0304

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00256

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00525

GnomAD4 exome AF: 0.00125 AC: 270 AN: 216472 Hom.: 4 Cov.: 2 AF XY: 0.00109 AC XY: 122 AN XY: 112110

Gnomad4 AFR exome AF: 0.0311

Gnomad4 AMR exome AF: 0.00236

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000118

Gnomad4 FIN exome AF: 0.000392

Gnomad4 NFE exome AF: 0.0000514

Gnomad4 OTH exome AF: 0.00325

GnomAD4 genome AF: 0.00868 AC: 1322 AN: 152298 Hom.: 25 Cov.: 32 AF XY: 0.00837 AC XY: 623 AN XY: 74468

Gnomad4 AFR AF: 0.0304

Gnomad4 AMR AF: 0.00255

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000735

Gnomad4 OTH AF: 0.00520

Alfa AF: 0.00424 Hom.: 1

Bravo AF: 0.00954

Asia WGS AF: 0.00173 AC: 6 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	May 16, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.5
DANN	Benign	0.57

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: rs77431018; hg19: chr12-94702389;