rs2274278

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_018191.4(RCBTB1):c.643C>T(p.Leu215Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.846 in 1,601,994 control chromosomes in the GnomAD database, including 573,484 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.85 ( 55192 hom., cov: 30)

Exomes 𝑓: 0.84 ( 518292 hom. )

Consequence

RCBTB1
NM_018191.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.881

Publications

23 publications found

Variant links:

Genes affected

RCBTB1 (HGNC:18243): (RCC1 and BTB domain containing protein 1) This gene encodes a protein with an N-terminal RCC1 domain and a C-terminal BTB (broad complex, tramtrack and bric-a-brac) domain. In rat, over-expression of this gene in vascular smooth muscle cells induced cellular hypertrophy. In rat, the C-terminus of RCBTB1 interacts with the angiotensin II receptor-1A. In humans, this gene maps to a region of chromosome 13q that is frequently deleted in B-cell chronic lymphocytic leukemia and other lymphoid malignancies. [provided by RefSeq, Jul 2008]

RCBTB1 Gene-Disease associations (from GenCC):

RCBTB1-related retinopathy
Inheritance: AR Classification: DEFINITIVE, STRONG, LIMITED Submitted by: Ambry Genetics, ClinGen, G2P, Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine
reticular dystrophy of the retinal pigment epithelium
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
exudative vitreoretinopathy
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics, G2P

RCBTB1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.44).

BP6

Variant 13-49552246-G-A is Benign according to our data. Variant chr13-49552246-G-A is described in ClinVar as Benign. ClinVar VariationId is 1170496.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.881 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.881 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RCBTB1	NM_018191.4 link	c.643C>T	p.Leu215Leu	synonymous_variant	Exon 7 of 13	ENST00000378302.7	NP_060661.3	Q8NDN9-1B3KR20

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
RCBTB1	ENST00000378302.7 link	c.643C>T	p.Leu215Leu	synonymous_variant	Exon 7 of 13	1	NM_018191.4	ENSP00000367552.2	Q8NDN9-1
RCBTB1	ENST00000258646.3 link	c.643C>T	p.Leu215Leu	synonymous_variant	Exon 5 of 11	2		ENSP00000258646.3	Q8NDN9-1
RCBTB1	ENST00000490058.1 link	n.7C>T		non_coding_transcript_exon_variant	Exon 1 of 2	2

Frequencies

GnomAD3 genomes

AF:

0.851

AC:

129286

AN:

151976

Hom.:

55125

Cov.:

show subpopulations

Gnomad AFR

AF:

0.888

Gnomad AMI

AF:

0.648

Gnomad AMR

AF:

0.865

Gnomad ASJ

AF:

0.796

Gnomad EAS

AF:

0.895

Gnomad SAS

AF:

0.827

Gnomad FIN

AF:

0.798

Gnomad MID

AF:

0.807

Gnomad NFE

AF:

0.837

Gnomad OTH

AF:

0.832

GnomAD2 exomes

AF:

0.847

AC:

197908

AN:

233604

AF XY:

0.842

show subpopulations

Gnomad AFR exome

AF:

0.893

Gnomad AMR exome

AF:

0.904

Gnomad ASJ exome

AF:

0.815

Gnomad EAS exome

AF:

0.893

Gnomad FIN exome

AF:

0.808

Gnomad NFE exome

AF:

0.835

Gnomad OTH exome

AF:

0.829

GnomAD4 exome

AF:

0.845

AC:

1225152

AN:

1449900

Hom.:

518292

Cov.:

AF XY:

0.843

AC XY:

607215

AN XY:

720072

show subpopulations

African (AFR)

AF:

0.884

AC:

29477

AN:

33356

American (AMR)

AF:

0.899

AC:

38979

AN:

43338

Ashkenazi Jewish (ASJ)

AF:

0.817

AC:

21072

AN:

25802

East Asian (EAS)

AF:

0.884

AC:

34948

AN:

39544

South Asian (SAS)

AF:

0.815

AC:

68593

AN:

84138

European-Finnish (FIN)

AF:

0.811

AC:

42590

AN:

52524

Middle Eastern (MID)

AF:

0.804

AC:

4520

AN:

5624

European-Non Finnish (NFE)

AF:

0.845

AC:

934185

AN:

1105636

Other (OTH)

AF:

0.847

AC:

50788

AN:

59938

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

8466

16933

25399

33866

42332

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21094

42188

63282

84376

105470

<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:

0.851

AC:

129413

AN:

152094

Hom.:

55192

Cov.:

AF XY:

0.848

AC XY:

63060

AN XY:

74334

show subpopulations

African (AFR)

AF:

0.888

AC:

36877

AN:

41518

American (AMR)

AF:

0.865

AC:

13207

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.796

AC:

2764

AN:

3472

East Asian (EAS)

AF:

0.895

AC:

4629

AN:

5170

South Asian (SAS)

AF:

0.828

AC:

3991

AN:

4818

European-Finnish (FIN)

AF:

0.798

AC:

8424

AN:

10550

Middle Eastern (MID)

AF:

0.803

AC:

236

AN:

294

European-Non Finnish (NFE)

AF:

0.837

AC:

56933

AN:

67986

Other (OTH)

AF:

0.833

AC:

1762

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

956

1912

2868

3824

4780

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

890

1780

2670

3560

4450

<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:

0.846

Hom.:

28188

Bravo

AF:

0.858

Asia WGS

AF:

0.862

AC:

2998

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Feb 07, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

RCBTB1-related retinopathy

Benign:1

Nov 07, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.44

CADD

Benign

7.7

(source)

DANN

Benign

0.74

PhyloP100

0.88

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=96/4

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over