rs869180248

chr12-88060817-T-TAAchr12-88060817-TAA-Tchr12-88060817-T-TAchr12-88060817-TA-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP6_Moderate

The NM_025114.4(CEP290):c.6522+12_6522+13insTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000586 in 1,410,258 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00065 (0 hom.)
• Consequence: CEP290 NM_025114.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.206

Genes affected

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]

LOC124902977 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 12-88060817-T-TAA is Benign according to our data. Variant chr12-88060817-T-TAA is described in ClinVar as [Benign]. Clinvar id is 2945757.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CEP290	NM_025114.4	c.6522+12_6522+13insTT		intron_variant		ENST00000552810.6
LOC124902977	XR_007063393.1	n.886+3804_886+3805dup		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CEP290	ENST00000552810.6	c.6522+12_6522+13insTT		intron_variant		1	NM_025114.4	P4

Frequencies

GnomAD3 genomes AF: 0.0000264 AC: 4 AN: 151490 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000243

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000442

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000653 AC: 822 AN: 1258656 Hom.: 0 Cov.: 29 AF XY: 0.000623 AC XY: 388 AN XY: 622318

Gnomad4 AFR exome AF: 0.000176

Gnomad4 AMR exome AF: 0.00244

Gnomad4 ASJ exome AF: 0.000580

Gnomad4 EAS exome AF: 0.00101

Gnomad4 SAS exome AF: 0.000884

Gnomad4 FIN exome AF: 0.000321

Gnomad4 NFE exome AF: 0.000619

Gnomad4 OTH exome AF: 0.000683

GnomAD4 genome AF: 0.0000264 AC: 4 AN: 151602 Hom.: 0 Cov.: 0 AF XY: 0.0000135 AC XY: 1 AN XY: 74084

Gnomad4 AFR AF: 0.0000242

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000442

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Meckel-Gruber syndrome;C0431399:Familial aplasia of the vermis;C0687120:Nephronophthisis Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 04, 2024

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Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs11405846; hg19: chr12-88454594;