NM_018191.4:c.990C>T

Variant names:

• chr13-49549513-G-A
• rs3751383
• NM_018191.4:c.990C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_018191.4(RCBTB1):​c.990C>T​(p.Asp330Asp) 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:3
• Conservation: PhyloP100: -0.935
• Publications: 22 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 -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 VariationId 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 rank	MANE	Protein	UniProt
RCBTB1	NM_018191.4	c.990C>T	p.Asp330Asp	synonymous_variant	Exon 9 of 13	ENST00000378302.7	NP_060661.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RCBTB1	ENST00000378302.7	c.990C>T	p.Asp330Asp	synonymous_variant	Exon 9 of 13	1	NM_018191.4	ENSP00000367552.2
RCBTB1	ENST00000258646.3	c.990C>T	p.Asp330Asp	synonymous_variant	Exon 7 of 11	2		ENSP00000258646.3

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

GnomAD2 exomes AF: 0.209 AC: 51858 AN: 248536 AF XY: 0.209

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 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

African (AFR) AF: 0.447 AC: 14939 AN: 33404

American (AMR) AF: 0.165 AC: 7374 AN: 44656

Ashkenazi Jewish (ASJ) AF: 0.155 AC: 4055 AN: 26126

East Asian (EAS) AF: 0.265 AC: 10518 AN: 39626

South Asian (SAS) AF: 0.308 AC: 26511 AN: 86164

European-Finnish (FIN) AF: 0.216 AC: 11555 AN: 53400

Middle Eastern (MID) AF: 0.155 AC: 894 AN: 5762

European-Non Finnish (NFE) AF: 0.143 AC: 158762 AN: 1111522

Other (OTH) AF: 0.183 AC: 11025 AN: 60354

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

African (AFR) AF: 0.438 AC: 18120 AN: 41340

American (AMR) AF: 0.155 AC: 2360 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.153 AC: 532 AN: 3472

East Asian (EAS) AF: 0.260 AC: 1336 AN: 5144

South Asian (SAS) AF: 0.317 AC: 1524 AN: 4802

European-Finnish (FIN) AF: 0.229 AC: 2415 AN: 10550

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.145 AC: 9869 AN: 67962

Other (OTH) AF: 0.190 AC: 401 AN: 2110

Alfa AF: 0.182 Hom.: 1562

Bravo AF: 0.243

Asia WGS AF: 0.308 AC: 1076 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

May 04, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	0.24
DANN	Benign	0.92
PhyloP100		-0.94
Mutation Taster		=92/8	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: rs3751383; hg19: chr13-50123649; COSMIC: COSV51633236; COSMIC: COSV51633236;