rs3186013

chr13-49533768-G-A

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
RCBTB1	NM_018191.4	c.*354C>T		3_prime_UTR_variant	13/13	ENST00000378302.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RCBTB1	ENST00000378302.7	c.*354C>T		3_prime_UTR_variant	13/13	1	NM_018191.4	P1
RCBTB1	ENST00000258646.3	c.*354C>T		3_prime_UTR_variant	11/11	2		P1

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

Gnomad4 AFR exome AF: 0.405

Gnomad4 AMR exome AF: 0.524

Gnomad4 ASJ exome AF: 0.590

Gnomad4 EAS exome AF: 0.490

Gnomad4 SAS exome AF: 0.347

Gnomad4 FIN exome AF: 0.583

Gnomad4 NFE exome AF: 0.551

Gnomad4 OTH exome AF: 0.559

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

Gnomad4 AFR AF: 0.365

Gnomad4 AMR AF: 0.521

Gnomad4 ASJ AF: 0.541

Gnomad4 EAS AF: 0.470

Gnomad4 SAS AF: 0.321

Gnomad4 FIN AF: 0.529

Gnomad4 NFE AF: 0.533

Gnomad4 OTH AF: 0.500

Alfa AF: 0.525 Hom.: 21393

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

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

LitVar

Other links and lift over

dbSNP: rs3186013; hg19: chr13-50107904;