13-49535448-C-T

Variant names:

• chr13-49535448-C-T
• rs1925742
• NM_018191.4:c.1456-1186G>A

Variant summary

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

The NM_018191.4(RCBTB1):​c.1456-1186G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.58 in 151,998 control chromosomes in the GnomAD database, including 26,728 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 0.58 (26728 hom., cov: 31)
• Consequence: RCBTB1 NM_018191.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.721
• Publications: 8 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.679 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RCBTB1	NM_018191.4	c.1456-1186G>A		intron_variant	Intron 12 of 12	ENST00000378302.7	NP_060661.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RCBTB1	ENST00000378302.7	c.1456-1186G>A		intron_variant	Intron 12 of 12	1	NM_018191.4	ENSP00000367552.2
RCBTB1	ENST00000258646.3	c.1456-1186G>A		intron_variant	Intron 10 of 10	2		ENSP00000258646.3
RCBTB1	ENST00000471984.1	n.344-1186G>A		intron_variant	Intron 2 of 2	3

Frequencies

GnomAD3 genomes AF: 0.580 AC: 88074 AN: 151880 Hom.: 26711 Cov.: 31

Gnomad AFR AF: 0.399

Gnomad AMI AF: 0.534

Gnomad AMR AF: 0.622

Gnomad ASJ AF: 0.638

Gnomad EAS AF: 0.517

Gnomad SAS AF: 0.471

Gnomad FIN AF: 0.612

Gnomad MID AF: 0.675

Gnomad NFE AF: 0.685

Gnomad OTH AF: 0.602

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.580 AC: 88129 AN: 151998 Hom.: 26728 Cov.: 31 AF XY: 0.574 AC XY: 42644 AN XY: 74314

African (AFR) AF: 0.399 AC: 16519 AN: 41436

American (AMR) AF: 0.622 AC: 9503 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.638 AC: 2212 AN: 3468

East Asian (EAS) AF: 0.518 AC: 2677 AN: 5168

South Asian (SAS) AF: 0.472 AC: 2278 AN: 4828

European-Finnish (FIN) AF: 0.612 AC: 6465 AN: 10566

Middle Eastern (MID) AF: 0.664 AC: 194 AN: 292

European-Non Finnish (NFE) AF: 0.685 AC: 46519 AN: 67942

Other (OTH) AF: 0.605 AC: 1276 AN: 2108

Alfa AF: 0.642 Hom.: 80259

Bravo AF: 0.576

Asia WGS AF: 0.488 AC: 1693 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.94
DANN	Benign	0.80
PhyloP100		-0.72
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: rs1925742; hg19: chr13-50109584;