rs3751383

chr13-49549513-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_018191.4(RCBTB1):c.990C>T(p.Asp330=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.175 in 1,612,872 control chromosomes in the GnomAD database, including 29,632 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.24 (5715 hom., cov: 31)
  • Exomes 𝑓: 0.17 (23917 hom.)
• Consequence: RCBTB1 NM_018191.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.935

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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP6: Variant 13-49549513-G-A is Benign according to our data. Variant chr13-49549513-G-A is described in ClinVar as [Benign]. Clinvar id is 1168540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.935 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.433 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RCBTB1	NM_018191.4	c.990C>T	p.Asp330=	synonymous_variant	9/13	ENST00000378302.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RCBTB1	ENST00000378302.7	c.990C>T	p.Asp330=	synonymous_variant	9/13	1	NM_018191.4	P1
RCBTB1	ENST00000258646.3	c.990C>T	p.Asp330=	synonymous_variant	7/11	2		P1

Frequencies

GnomAD3 genomes AF: 0.242 AC: 36733 AN: 151740 Hom.: 5704 Cov.: 31

Gnomad AFR AF: 0.438

Gnomad AMI AF: 0.195

Gnomad AMR AF: 0.155

Gnomad ASJ AF: 0.153

Gnomad EAS AF: 0.260

Gnomad SAS AF: 0.317

Gnomad FIN AF: 0.229

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.145

Gnomad OTH AF: 0.193

GnomAD3 exomes AF: 0.209 AC: 51858 AN: 248536 Hom.: 6335 AF XY: 0.209 AC XY: 28080 AN XY: 134336

Gnomad AFR exome AF: 0.449

Gnomad AMR exome AF: 0.172

Gnomad ASJ exome AF: 0.157

Gnomad EAS exome AF: 0.255

Gnomad SAS exome AF: 0.317

Gnomad FIN exome AF: 0.222

Gnomad NFE exome AF: 0.152

Gnomad OTH exome AF: 0.173

GnomAD4 exome AF: 0.168 AC: 245633 AN: 1461014 Hom.: 23917 Cov.: 36 AF XY: 0.171 AC XY: 124540 AN XY: 726760

Gnomad4 AFR exome AF: 0.447

Gnomad4 AMR exome AF: 0.165

Gnomad4 ASJ exome AF: 0.155

Gnomad4 EAS exome AF: 0.265

Gnomad4 SAS exome AF: 0.308

Gnomad4 FIN exome AF: 0.216

Gnomad4 NFE exome AF: 0.143

Gnomad4 OTH exome AF: 0.183

GnomAD4 genome AF: 0.242 AC: 36779 AN: 151858 Hom.: 5715 Cov.: 31 AF XY: 0.246 AC XY: 18230 AN XY: 74214

Gnomad4 AFR AF: 0.438

Gnomad4 AMR AF: 0.155

Gnomad4 ASJ AF: 0.153

Gnomad4 EAS AF: 0.260

Gnomad4 SAS AF: 0.317

Gnomad4 FIN AF: 0.229

Gnomad4 NFE AF: 0.145

Gnomad4 OTH AF: 0.190

Alfa AF: 0.177 Hom.: 1056

Bravo AF: 0.243

Asia WGS AF: 0.308 AC: 1076 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 04, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
Cadd	Benign	0.24
Dann	Benign	0.92

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: rs3751383; hg19: chr13-50123649; COSMIC: COSV51633236; COSMIC: COSV51633236;