Genetic Variant NM_018191.4:c.*354C>T (chr13-49533768-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_018191.4(RCBTB1):c.*354C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.479 in 160,964 control chromosomes in the GnomAD database, including 18,973 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.48 ( 17647 hom., cov: 31)

Exomes 𝑓: 0.54 ( 1326 hom. )

Consequence

RCBTB1
NM_018191.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.689

Publications

14 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.528 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RCBTB1	NM_018191.4 link	c.*354C>T		3_prime_UTR_variant	Exon 13 of 13	ENST00000378302.7	NP_060661.3	Q8NDN9-1B3KR20

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
RCBTB1	ENST00000378302.7 link	c.*354C>T	3_prime_UTR_variant	Exon 13 of 13	1	NM_018191.4	ENSP00000367552.2	Q8NDN9-1
RCBTB1	ENST00000258646.3 link	c.*354C>T	3_prime_UTR_variant	Exon 11 of 11	2		ENSP00000258646.3	Q8NDN9-1
RCBTB1	ENST00000471984.1 link	n.*150C>T	downstream_gene_variant		3

Frequencies

GnomAD3 genomes

AF:

0.476

AC:

72272

AN:

151792

Hom.:

17635

Cov.:

show subpopulations

Gnomad AFR

AF:

0.365

Gnomad AMI

AF:

0.433

Gnomad AMR

AF:

0.520

Gnomad ASJ

AF:

0.541

Gnomad EAS

AF:

0.469

Gnomad SAS

AF:

0.321

Gnomad FIN

AF:

0.529

Gnomad MID

AF:

0.598

Gnomad NFE

AF:

0.533

Gnomad OTH

AF:

0.503

GnomAD4 exome

AF:

0.536

AC:

4850

AN:

9054

Hom.:

1326

Cov.:

AF XY:

0.539

AC XY:

2504

AN XY:

4642

show subpopulations

African (AFR)

AF:

0.405

AC:

136

AN:

336

American (AMR)

AF:

0.524

AC:

262

AN:

500

Ashkenazi Jewish (ASJ)

AF:

0.590

AC:

204

AN:

346

East Asian (EAS)

AF:

0.490

AC:

191

AN:

390

South Asian (SAS)

AF:

0.347

AC:

129

AN:

372

European-Finnish (FIN)

AF:

0.583

AC:

189

AN:

324

Middle Eastern (MID)

AF:

0.469

AC:

AN:

European-Non Finnish (NFE)

AF:

0.551

AC:

3391

AN:

6158

Other (OTH)

AF:

0.559

AC:

333

AN:

596

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

Heterozygous variant carriers

108

216

323

431

539

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

128

160

<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:

0.476

AC:

72320

AN:

151910

Hom.:

17647

Cov.:

AF XY:

0.473

AC XY:

35085

AN XY:

74200

show subpopulations

African (AFR)

AF:

0.365

AC:

15131

AN:

41404

American (AMR)

AF:

0.521

AC:

7946

AN:

15254

Ashkenazi Jewish (ASJ)

AF:

0.541

AC:

1880

AN:

3472

East Asian (EAS)

AF:

0.470

AC:

2418

AN:

5148

South Asian (SAS)

AF:

0.321

AC:

1547

AN:

4822

European-Finnish (FIN)

AF:

0.529

AC:

5559

AN:

10514

Middle Eastern (MID)

AF:

0.595

AC:

175

AN:

294

European-Non Finnish (NFE)

AF:

0.533

AC:

36212

AN:

67978

Other (OTH)

AF:

0.500

AC:

1057

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1914

3828

5741

7655

9569

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

650

1300

1950

2600

3250

<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:

0.519

Hom.:

27331

Bravo

AF:

0.476

Asia WGS

AF:

0.390

AC:

1353

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

5.1

(source)

DANN

Benign

0.56

PhyloP100

0.69

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over