rs3186013

Variant names:

• chr13-49533768-G-A
• rs3186013
• NM_018191.4:c.*354C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.689
• Publications: 14 publications found

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

ACMG classification

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	c.*354C>T		3_prime_UTR_variant	Exon 13 of 13	ENST00000378302.7	NP_060661.3

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.476 AC: 72272 AN: 151792 Hom.: 17635 Cov.: 31

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.: 0 AF XY: 0.539 AC XY: 2504 AN XY: 4642

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: 15 AN: 32

European-Non Finnish (NFE) AF: 0.551 AC: 3391 AN: 6158

Other (OTH) AF: 0.559 AC: 333 AN: 596

GnomAD4 genome AF: 0.476 AC: 72320 AN: 151910 Hom.: 17647 Cov.: 31 AF XY: 0.473 AC XY: 35085 AN XY: 74200

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

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
DANN	Benign	0.56
PhyloP100		0.69
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3186013; hg19: chr13-50107904;