rs7981396

Variant names:

• chr13-49577790-C-T
• rs7981396
• NM_018191.4:c.-42+2715G>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.-42+2715G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.223 in 152,092 control chromosomes in the GnomAD database, including 4,656 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 0.22 (4656 hom., cov: 33)
• Consequence: RCBTB1 NM_018191.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.39
• Publications: 5 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.532 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018191.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RCBTB1	NM_018191.4	MANE Select	c.-42+2715G>A		intron	N/A	NP_060661.3
	RCBTB1	NM_001352500.2		c.-45+2715G>A		intron	N/A	NP_001339429.1
	RCBTB1	NM_001352501.2		c.-42+7654G>A		intron	N/A	NP_001339430.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RCBTB1	ENST00000378302.7	TSL:1 MANE Select	c.-42+2715G>A		intron	N/A	ENSP00000367552.2

Frequencies

GnomAD3 genomes AF: 0.223 AC: 33857 AN: 151974 Hom.: 4641 Cov.: 33

Gnomad AFR AF: 0.321

Gnomad AMI AF: 0.165

Gnomad AMR AF: 0.254

Gnomad ASJ AF: 0.238

Gnomad EAS AF: 0.548

Gnomad SAS AF: 0.325

Gnomad FIN AF: 0.219

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.125

Gnomad OTH AF: 0.207

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

GnomAD4 genome AF: 0.223 AC: 33909 AN: 152092 Hom.: 4656 Cov.: 33 AF XY: 0.231 AC XY: 17172 AN XY: 74346

African (AFR) AF: 0.321 AC: 13302 AN: 41460

American (AMR) AF: 0.254 AC: 3882 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.238 AC: 826 AN: 3470

East Asian (EAS) AF: 0.549 AC: 2837 AN: 5170

South Asian (SAS) AF: 0.325 AC: 1569 AN: 4824

European-Finnish (FIN) AF: 0.219 AC: 2315 AN: 10566

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.126 AC: 8534 AN: 67998

Other (OTH) AF: 0.205 AC: 434 AN: 2114

Alfa AF: 0.201 Hom.: 609

Bravo AF: 0.233

Asia WGS AF: 0.430 AC: 1494 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.0
DANN	Benign	0.80
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs7981396; hg19: chr13-50151926;