chr13-49572410-A-C

Position:

• chr13-49572410-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018191.4(RCBTB1):​c.-41-5090T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.032 in 152,284 control chromosomes in the GnomAD database, including 192 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 0.032 (192 hom., cov: 32)
• Consequence: RCBTB1 NM_018191.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.106

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=-0.87).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.109 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RCBTB1	NM_018191.4	c.-41-5090T>G		intron_variant		ENST00000378302.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RCBTB1	ENST00000378302.7	c.-41-5090T>G		intron_variant		1	NM_018191.4	P1

Frequencies

GnomAD3 genomes AF: 0.0320 AC: 4864 AN: 152166 Hom.: 187 Cov.: 32

Gnomad AFR AF: 0.00734

Gnomad AMI AF: 0.0164

Gnomad AMR AF: 0.113

Gnomad ASJ AF: 0.0490

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.0369

Gnomad FIN AF: 0.0288

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0307

Gnomad OTH AF: 0.0229

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

GnomAD4 genome AF: 0.0320 AC: 4875 AN: 152284 Hom.: 192 Cov.: 32 AF XY: 0.0335 AC XY: 2497 AN XY: 74456

Gnomad4 AFR AF: 0.00732

Gnomad4 AMR AF: 0.114

Gnomad4 ASJ AF: 0.0490

Gnomad4 EAS AF: 0.00154

Gnomad4 SAS AF: 0.0367

Gnomad4 FIN AF: 0.0288

Gnomad4 NFE AF: 0.0307

Gnomad4 OTH AF: 0.0227

Alfa AF: 0.0349 Hom.: 19

Bravo AF: 0.0383

Asia WGS AF: 0.0250 AC: 86 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	7.0
DANN	Benign	0.91

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7329797; hg19: chr13-50146546;