rs45613639

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The ENST00000550333.5(RLIG1):n.*1757A>G 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 0.0192 in 1,180,658 control chromosomes in the GnomAD database, including 294 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.016 ( 27 hom., cov: 32)

Exomes 𝑓: 0.020 ( 267 hom. )

Consequence

RLIG1
ENST00000550333.5 non_coding_transcript_exon

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 1.04

Publications

4 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.73).

BP6

Variant 12-88049436-A-G is Benign according to our data. Variant chr12-88049436-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 126268.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.0159 (2414/152132) while in subpopulation EAS AF = 0.0228 (118/5176). AF 95% confidence interval is 0.0203. There are 27 homozygotes in GnomAd4. There are 1197 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 27 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RLIG1	NM_001009894.3 link	c.*1014A>G		3_prime_UTR_variant	Exon 7 of 7	ENST00000356891.4	NP_001009894.2
CEP290	NM_025114.4 link	c.7210-22T>C		intron_variant	Intron 53 of 53	ENST00000552810.6	NP_079390.3	O15078Q05BJ6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RLIG1	ENST00000356891.4 link	c.*1014A>G		3_prime_UTR_variant	Exon 7 of 7	1	NM_001009894.3	ENSP00000349358.3		Q8N999-1
CEP290	ENST00000552810.6 link	c.7210-22T>C		intron_variant	Intron 53 of 53	1	NM_025114.4	ENSP00000448012.1		O15078

Frequencies

GnomAD3 genomes

AF:

0.0159

AC:

2410

AN:

152014

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00722

Gnomad AMI

AF:

0.0296

Gnomad AMR

AF:

0.0223

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.0227

Gnomad SAS

AF:

0.00289

Gnomad FIN

AF:

0.0259

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0189

Gnomad OTH

AF:

0.0230

GnomAD2 exomes

AF:

0.0153

AC:

2037

AN:

132878

AF XY:

0.0150

show subpopulations

Gnomad AFR exome

AF:

0.00537

Gnomad AMR exome

AF:

0.0164

Gnomad ASJ exome

AF:

0.00132

Gnomad EAS exome

AF:

0.0145

Gnomad FIN exome

AF:

0.0253

Gnomad NFE exome

AF:

0.0192

Gnomad OTH exome

AF:

0.0157

GnomAD4 exome

AF:

0.0196

AC:

20199

AN:

1028526

Hom.:

267

Cov.:

AF XY:

0.0192

AC XY:

10033

AN XY:

523214

show subpopulations

African (AFR)

AF:

0.00635

AC:

144

AN:

22664

American (AMR)

AF:

0.0161

AC:

388

AN:

24032

Ashkenazi Jewish (ASJ)

AF:

0.00135

AC:

AN:

21534

East Asian (EAS)

AF:

0.0394

AC:

1358

AN:

34470

South Asian (SAS)

AF:

0.00353

AC:

231

AN:

65458

European-Finnish (FIN)

AF:

0.0237

AC:

1176

AN:

49610

Middle Eastern (MID)

AF:

0.00481

AC:

AN:

3326

European-Non Finnish (NFE)

AF:

0.0211

AC:

16096

AN:

762460

Other (OTH)

AF:

0.0169

AC:

761

AN:

44972

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1005

2010

3014

4019

5024

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

568

1136

1704

2272

2840

<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:

0.0159

AC:

2414

AN:

152132

Hom.:

Cov.:

AF XY:

0.0161

AC XY:

1197

AN XY:

74362

show subpopulations

African (AFR)

AF:

0.00729

AC:

303

AN:

41558

American (AMR)

AF:

0.0223

AC:

340

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.00115

AC:

AN:

3470

East Asian (EAS)

AF:

0.0228

AC:

118

AN:

5176

South Asian (SAS)

AF:

0.00290

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.0259

AC:

275

AN:

10610

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0189

AC:

1284

AN:

67894

Other (OTH)

AF:

0.0227

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

123

246

369

492

615

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

150

<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:

0.0149

Hom.:

Bravo

AF:

0.0143

Asia WGS

AF:

0.0110

AC:

AN:

3466

ClinVar

Significance: Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Genetic Services Laboratory, University of Chicago

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -

not provided

Benign:2

Jul 27, 2018

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

8.5

(source)

DANN

Benign

0.85

PhyloP100

1.0

BranchPoint Hunter

2.0

Mutation Taster

=99/1

polymorphism

(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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over