12-88060817-TAA-TAAA

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_025114.4(CEP290):c.6522+12dupT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.886 in 1,417,558 control chromosomes in the GnomAD database, including 566,175 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.78 ( 50000 hom., cov: 0)

Exomes 𝑓: 0.90 ( 516175 hom. )

Consequence

CEP290
NM_025114.4 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:16

Conservation

PhyloP100: -0.206

Publications

6 publications found

Variant links:

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]

CEP290 Gene-Disease associations (from GenCC):

CEP290-related ciliopathy
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
Joubert syndrome 5
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
Bardet-Biedl syndrome 14
Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp
Leber congenital amaurosis 10
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
Leber congenital amaurosis
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Bardet-Biedl syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
Joubert syndrome with oculorenal defect
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
Meckel syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
Senior-Loken syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

CEP290 links:

LOC124902977 (HGNC:):

LOC124902977 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP6

Variant 12-88060817-T-TA is Benign according to our data. Variant chr12-88060817-T-TA is described in ClinVar as Benign. ClinVar VariationId is 166828.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.94 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025114.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP290	NM_025114.4	MANE Select	c.6522+12dupT		intron	N/A	NP_079390.3	O15078

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CEP290	ENST00000552810.6	TSL:1 MANE Select	c.6522+12_6522+13insT	intron	N/A	ENSP00000448012.1	O15078
CEP290	ENST00000547691.8	TSL:1	c.3804+12_3804+13insT	intron	N/A	ENSP00000446905.3	A0A5K1VW81
CEP290	ENST00000675476.1		c.7383+12_7383+13insT	intron	N/A	ENSP00000502161.1	A0A6Q8PGB1

Frequencies

GnomAD3 genomes

AF:

0.779

AC:

118028

AN:

151442

Hom.:

50000

Cov.:

show subpopulations

Gnomad AFR

AF:

0.409

Gnomad AMI

AF:

0.921

Gnomad AMR

AF:

0.865

Gnomad ASJ

AF:

0.894

Gnomad EAS

AF:

0.962

Gnomad SAS

AF:

0.896

Gnomad FIN

AF:

0.962

Gnomad MID

AF:

0.921

Gnomad NFE

AF:

0.925

Gnomad OTH

AF:

0.818

GnomAD2 exomes

AF:

0.882

AC:

98803

AN:

112070

AF XY:

0.889

show subpopulations

Gnomad AFR exome

AF:

0.379

Gnomad AMR exome

AF:

0.885

Gnomad ASJ exome

AF:

0.897

Gnomad EAS exome

AF:

0.959

Gnomad FIN exome

AF:

0.958

Gnomad NFE exome

AF:

0.917

Gnomad OTH exome

AF:

0.879

GnomAD4 exome

AF:

0.899

AC:

1138572

AN:

1266002

Hom.:

516175

Cov.:

AF XY:

0.900

AC XY:

563370

AN XY:

625892

show subpopulations

African (AFR)

AF:

0.379

AC:

10793

AN:

28458

American (AMR)

AF:

0.883

AC:

18226

AN:

20640

Ashkenazi Jewish (ASJ)

AF:

0.892

AC:

20112

AN:

22548

East Asian (EAS)

AF:

0.941

AC:

30870

AN:

32806

South Asian (SAS)

AF:

0.880

AC:

58054

AN:

65972

European-Finnish (FIN)

AF:

0.955

AC:

44889

AN:

47006

Middle Eastern (MID)

AF:

0.891

AC:

4677

AN:

5252

European-Non Finnish (NFE)

AF:

0.913

AC:

904553

AN:

990336

Other (OTH)

AF:

0.876

AC:

46398

AN:

52984

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

4396

8791

13187

17582

21978

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19154

38308

57462

76616

95770

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.779

AC:

118041

AN:

151556

Hom.:

50000

Cov.:

AF XY:

0.785

AC XY:

58136

AN XY:

74056

show subpopulations

African (AFR)

AF:

0.408

AC:

16840

AN:

41274

American (AMR)

AF:

0.865

AC:

13186

AN:

15250

Ashkenazi Jewish (ASJ)

AF:

0.894

AC:

3102

AN:

3470

East Asian (EAS)

AF:

0.962

AC:

4930

AN:

5124

South Asian (SAS)

AF:

0.897

AC:

4301

AN:

4794

European-Finnish (FIN)

AF:

0.962

AC:

10045

AN:

10442

Middle Eastern (MID)

AF:

0.918

AC:

270

AN:

294

European-Non Finnish (NFE)

AF:

0.925

AC:

62809

AN:

67898

Other (OTH)

AF:

0.819

AC:

1720

AN:

2100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

900

1799

2699

3598

4498

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

830

1660

2490

3320

4150

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.834

Hom.:

5695

Asia WGS

AF:

0.880

AC:

3030

AN:

3446

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (5)

Bardet-Biedl syndrome (1)

Bardet-Biedl syndrome 14 (1)

Joubert syndrome (1)

Joubert syndrome 5 (1)

Leber congenital amaurosis (1)

Meckel syndrome, type 4 (1)

Meckel-Gruber syndrome (1)

Meckel-Gruber syndrome;C0687120:Nephronophthisis;C5979921:Joubert syndrome (1)

not provided (1)

Renal dysplasia and retinal aplasia (1)

Senior-Loken syndrome 6 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.21

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over