12-88131237-A-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_025114.4(CEP290):c.442-19T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0341 in 1,457,462 control chromosomes in the GnomAD database, including 1,213 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.052 ( 313 hom., cov: 31)

Exomes 𝑓: 0.032 ( 900 hom. )

Consequence

CEP290
NM_025114.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 2.31

Publications

4 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.52).

BP6

Variant 12-88131237-A-T is Benign according to our data. Variant chr12-88131237-A-T is described in ClinVar as Benign. ClinVar VariationId is 126259.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.106 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.442-19T>A		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.442-19T>A	intron	N/A	ENSP00000448012.1	O15078
CEP290	ENST00000547926.7	TSL:1	n.442-19T>A	intron	N/A	ENSP00000448573.3	F8VS29
CEP290	ENST00000675476.1		c.442-19T>A	intron	N/A	ENSP00000502161.1	A0A6Q8PGB1

Frequencies

GnomAD3 genomes

AF:

0.0515

AC:

7743

AN:

150430

Hom.:

310

Cov.:

show subpopulations

Gnomad AFR

AF:

0.108

Gnomad AMI

AF:

0.0297

Gnomad AMR

AF:

0.0386

Gnomad ASJ

AF:

0.0574

Gnomad EAS

AF:

0.0293

Gnomad SAS

AF:

0.0199

Gnomad FIN

AF:

0.0273

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.0275

Gnomad OTH

AF:

0.0516

GnomAD2 exomes

AF:

0.0344

AC:

2956

AN:

86040

AF XY:

0.0319

show subpopulations

Gnomad AFR exome

AF:

0.114

Gnomad AMR exome

AF:

0.0341

Gnomad ASJ exome

AF:

0.0641

Gnomad EAS exome

AF:

0.0211

Gnomad FIN exome

AF:

0.0274

Gnomad NFE exome

AF:

0.0308

Gnomad OTH exome

AF:

0.0371

GnomAD4 exome

AF:

0.0320

AC:

41876

AN:

1306916

Hom.:

900

Cov.:

AF XY:

0.0317

AC XY:

20445

AN XY:

644236

show subpopulations

African (AFR)

AF:

0.113

AC:

2926

AN:

25904

American (AMR)

AF:

0.0292

AC:

530

AN:

18130

Ashkenazi Jewish (ASJ)

AF:

0.0590

AC:

1291

AN:

21882

East Asian (EAS)

AF:

0.0449

AC:

1451

AN:

32288

South Asian (SAS)

AF:

0.0173

AC:

1130

AN:

65340

European-Finnish (FIN)

AF:

0.0254

AC:

1214

AN:

47828

Middle Eastern (MID)

AF:

0.0298

AC:

133

AN:

4460

European-Non Finnish (NFE)

AF:

0.0302

AC:

31276

AN:

1037076

Other (OTH)

AF:

0.0356

AC:

1925

AN:

54008

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

1737

3474

5211

6948

8685

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1300

2600

3900

5200

6500

<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:

0.0515

AC:

7756

AN:

150546

Hom.:

313

Cov.:

AF XY:

0.0515

AC XY:

3779

AN XY:

73448

show subpopulations

African (AFR)

AF:

0.108

AC:

4457

AN:

41128

American (AMR)

AF:

0.0386

AC:

577

AN:

14954

Ashkenazi Jewish (ASJ)

AF:

0.0574

AC:

199

AN:

3464

East Asian (EAS)

AF:

0.0294

AC:

149

AN:

5076

South Asian (SAS)

AF:

0.0195

AC:

AN:

4724

European-Finnish (FIN)

AF:

0.0273

AC:

277

AN:

10156

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0276

AC:

1868

AN:

67764

Other (OTH)

AF:

0.0511

AC:

106

AN:

2076

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.517

Heterozygous variant carriers

347

694

1040

1387

1734

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

184

276

368

460

<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:

0.0443

Hom.:

Bravo

AF:

0.0540

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (5)

not provided (2)

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

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

6.2

(source)

DANN

Benign

0.38

PhyloP100

2.3

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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