12-88049161-GAAAC-G

Position:

• chr12-88049161-GAAAC-G

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_025114.4(CEP290):​c.*19_*22del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0101 in 1,412,030 control chromosomes in the GnomAD database, including 1,150 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.051 (665 hom., cov: 32)
  • Exomes 𝑓: 0.0051 (485 hom.)
• Consequence: CEP290 NM_025114.4 3_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 1.81

Genes affected

RLIG1 (HGNC:25322): (RNA 5'-phosphate and 3'-OH ligase 1) Predicted to act upstream of or within hematopoietic progenitor cell differentiation. [provided by Alliance of Genome Resources, Apr 2022]

CEP290 (HGNC:29021): (centrosomal protein 290) This gene encodes a protein with 13 putative coiled-coil domains, a region with homology to SMC chromosome segregation ATPases, six KID motifs, three tropomyosin homology domains and an ATP/GTP binding site motif A. The protein is localized to the centrosome and cilia and has sites for N-glycosylation, tyrosine sulfation, phosphorylation, N-myristoylation, and amidation. Mutations in this gene have been associated with Joubert syndrome and nephronophthisis and the presence of antibodies against this protein is associated with several forms of cancer. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant 12-88049161-GAAAC-G is Benign according to our data. Variant chr12-88049161-GAAAC-G is described in ClinVar as [Likely_benign]. Clinvar id is 261823.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.174 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RLIG1	NM_001009894.3	c.*743_*746del		3_prime_UTR_variant	7/7	ENST00000356891.4
CEP290	NM_025114.4	c.*19_*22del		3_prime_UTR_variant	54/54	ENST00000552810.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RLIG1	ENST00000356891.4	c.*743_*746del		3_prime_UTR_variant	7/7	1	NM_001009894.3	P1
CEP290	ENST00000552810.6	c.*19_*22del		3_prime_UTR_variant	54/54	1	NM_025114.4	P4

Frequencies

GnomAD3 genomes AF: 0.0512 AC: 7774 AN: 151832 Hom.: 664 Cov.: 32

Gnomad AFR AF: 0.177

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0211

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00662

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000354

Gnomad OTH AF: 0.0316

GnomAD3 exomes AF: 0.0138 AC: 2889 AN: 209598 Hom.: 234 AF XY: 0.0105 AC XY: 1212 AN XY: 115116

Gnomad AFR exome AF: 0.177

Gnomad AMR exome AF: 0.00723

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00511

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000230

Gnomad OTH exome AF: 0.00655

GnomAD4 exome AF: 0.00508 AC: 6406 AN: 1260080 Hom.: 485 AF XY: 0.00464 AC XY: 2939 AN XY: 632994

Gnomad4 AFR exome AF: 0.179

Gnomad4 AMR exome AF: 0.00924

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00544

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000145

Gnomad4 OTH exome AF: 0.0110

GnomAD4 genome AF: 0.0512 AC: 7786 AN: 151950 Hom.: 665 Cov.: 32 AF XY: 0.0496 AC XY: 3683 AN XY: 74276

Gnomad4 AFR AF: 0.177

Gnomad4 AMR AF: 0.0211

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00684

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000354

Gnomad4 OTH AF: 0.0313

Alfa AF: 0.0244 Hom.: 44

Bravo AF: 0.0583

Asia WGS AF: 0.00985 AC: 34 AN: 3466

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

Leber congenital amaurosis Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 10, 2018

- -

Meckel-Gruber syndrome Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Renal dysplasia and retinal aplasia Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Familial aplasia of the vermis Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Bardet-Biedl syndrome Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

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: rs142288119; hg19: chr12-88442938;