rs7981396

Positions:

• chr13-49577790-C-T

Variant summary

Our verdict is Benign. Variant got -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

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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.532 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RCBTB1	NM_018191.4	c.-42+2715G>A		intron_variant		ENST00000378302.7	NP_060661.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RCBTB1	ENST00000378302.7	c.-42+2715G>A		intron_variant		1	NM_018191.4	ENSP00000367552	P1

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

Gnomad4 AFR AF: 0.321

Gnomad4 AMR AF: 0.254

Gnomad4 ASJ AF: 0.238

Gnomad4 EAS AF: 0.549

Gnomad4 SAS AF: 0.325

Gnomad4 FIN AF: 0.219

Gnomad4 NFE AF: 0.126

Gnomad4 OTH AF: 0.205

Alfa AF: 0.198 Hom.: 570

Bravo AF: 0.233

Asia WGS AF: 0.430 AC: 1494 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.0
DANN	Benign	0.80

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7981396; hg19: chr13-50151926;