12-94331825-A-G

Variant names:

• chr12-94331825-A-G
• rs199593910
• NM_016122.3:c.1582T>C

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS1

The NM_016122.3(CEP83):​c.1582T>C​(p.Leu528Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000318 in 1,611,906 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0019 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00015 (0 hom.)
• Consequence: CEP83 NM_016122.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0200
• Publications: 1 publications found

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 Gene-Disease associations (from GenCC):

• nephronophthisis 18

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Genomics England PanelApp, G2P
• nephronophthisis 2

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 12-94331825-A-G is Benign according to our data. Variant chr12-94331825-A-G is described in ClinVar as Benign. ClinVar VariationId is 474963.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.02 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00189 (288/152302) while in subpopulation AFR AF = 0.00657 (273/41558). AF 95% confidence interval is 0.00593. There are 0 homozygotes in GnomAd4. There are 133 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016122.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP83	NM_016122.3	MANE Select	c.1582T>C	p.Leu528Leu	synonymous	Exon 14 of 17	NP_057206.2
	CEP83	NM_001042399.2		c.1582T>C	p.Leu528Leu	synonymous	Exon 13 of 16	NP_001035858.1
	CEP83	NM_001346457.2		c.1582T>C	p.Leu528Leu	synonymous	Exon 13 of 17	NP_001333386.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP83	ENST00000397809.10	TSL:1 MANE Select	c.1582T>C	p.Leu528Leu	synonymous	Exon 14 of 17	ENSP00000380911.4
	CEP83	ENST00000339839.9	TSL:1	c.1582T>C	p.Leu528Leu	synonymous	Exon 13 of 16	ENSP00000344655.5
	CEP83	ENST00000547232.5	TSL:1	n.1483T>C		non_coding_transcript_exon	Exon 14 of 17	ENSP00000447783.1

Frequencies

GnomAD3 genomes AF: 0.00189 AC: 287 AN: 152184 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00656

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000720

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: 0.0000147

Gnomad OTH AF: 0.00143

GnomAD2 exomes AF: 0.000445 AC: 111 AN: 249302 AF XY: 0.000318

Gnomad AFR exome AF: 0.00588

Gnomad AMR exome AF: 0.000464

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000884

Gnomad OTH exome AF: 0.000496

GnomAD4 exome AF: 0.000154 AC: 225 AN: 1459604 Hom.: 0 Cov.: 28 AF XY: 0.000120 AC XY: 87 AN XY: 726290

African (AFR) AF: 0.00505 AC: 169 AN: 33436

American (AMR) AF: 0.000537 AC: 24 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39672

South Asian (SAS) AF: 0.00 AC: 0 AN: 86202

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53364

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5754

European-Non Finnish (NFE) AF: 0.0000108 AC: 12 AN: 1110028

Other (OTH) AF: 0.000332 AC: 20 AN: 60306

GnomAD4 genome AF: 0.00189 AC: 288 AN: 152302 Hom.: 0 Cov.: 31 AF XY: 0.00179 AC XY: 133 AN XY: 74468

African (AFR) AF: 0.00657 AC: 273 AN: 41558

American (AMR) AF: 0.000719 AC: 11 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68024

Other (OTH) AF: 0.00142 AC: 3 AN: 2114

Alfa AF: 0.000916 Hom.: 1

Bravo AF: 0.00206

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Nephronophthisis 18 Benign:1

Jan 24, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	2.3
DANN	Benign	0.72
PhyloP100		-0.020
PromoterAI		-0.013	Neutral

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

Other links and lift over

dbSNP: rs199593910; hg19: chr12-94725601; COSMIC: COSV100353409; COSMIC: COSV100353409;