rs142288119

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

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

The ENST00000550333.5(RLIG1):n.*1486_*1489delCAAA variant causes a non coding transcript exon 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

RLIG1
ENST00000550333.5 non_coding_transcript_exon

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 1.81

Publications

0 publications found

Variant links:

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]

RLIG1 links:

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: Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
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 -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 Benign/Likely_benign. ClinVar VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000550333.5. 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
	CEP290	NM_025114.4	MANE Select	c.19_22delGTTT		3_prime_UTR	Exon 54 of 54	NP_079390.3
	RLIG1	NM_001009894.3	MANE Select	c.743_746delCAAA		3_prime_UTR	Exon 7 of 7	NP_001009894.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
RLIG1	ENST00000550333.5	TSL:1	n.1486_1489delCAAA	non_coding_transcript_exon	Exon 6 of 6	ENSP00000448194.1
RLIG1	ENST00000552121.5	TSL:1	n.1288_1291delCAAA	non_coding_transcript_exon	Exon 5 of 5	ENSP00000447327.1
CEP290	ENST00000552810.6	TSL:1 MANE Select	c.19_22delGTTT	3_prime_UTR	Exon 54 of 54	ENSP00000448012.1

Frequencies

GnomAD3 genomes

AF:

0.0512

AC:

7774

AN:

151832

Hom.:

664

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.0138

AC:

2889

AN:

209598

AF XY:

0.0105

show subpopulations

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 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

show subpopulations

African (AFR)

AF:

0.179

AC:

4978

AN:

27846

American (AMR)

AF:

0.00924

AC:

296

AN:

32030

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22932

East Asian (EAS)

AF:

0.00

AC:

AN:

38126

South Asian (SAS)

AF:

0.00544

AC:

394

AN:

72458

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52112

Middle Eastern (MID)

AF:

0.00388

AC:

AN:

3604

European-Non Finnish (NFE)

AF:

0.000145

AC:

139

AN:

957932

Other (OTH)

AF:

0.0110

AC:

585

AN:

53040

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

259

518

776

1035

1294

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

154

308

462

616

770

<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:

0.0512

AC:

7786

AN:

151950

Hom.:

665

Cov.:

AF XY:

0.0496

AC XY:

3683

AN XY:

74276

show subpopulations

African (AFR)

AF:

0.177

AC:

7341

AN:

41458

American (AMR)

AF:

0.0211

AC:

322

AN:

15256

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5172

South Asian (SAS)

AF:

0.00684

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10582

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000354

AC:

AN:

67868

Other (OTH)

AF:

0.0313

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

312

624

937

1249

1561

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

144

216

288

360

<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:

0.0244

Hom.:

Bravo

AF:

0.0583

Asia WGS

AF:

0.00985

AC:

AN:

3466

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Joubert syndrome

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Leber congenital amaurosis

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

not provided

Benign:1

May 10, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Meckel-Gruber syndrome

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Renal dysplasia and retinal aplasia

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Bardet-Biedl syndrome

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.8

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over