rs7329797

Variant names:

• chr13-49572410-A-C
• rs7329797
• NM_018191.4:c.-41-5090T>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 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: Labcorp Genetics (formerly Invitae), G2P, ClinGen, Ambry Genetics, 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: G2P, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RCBTB1	NM_018191.4	MANE Select	c.-41-5090T>G		intron	N/A	NP_060661.3
	RCBTB1	NM_001352500.2		c.-44-5087T>G		intron	N/A	NP_001339429.1	Q8NDN9-1
	RCBTB1	NM_001352501.2		c.-41-5090T>G		intron	N/A	NP_001339430.1	Q8NDN9-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RCBTB1	ENST00000378302.7	TSL:1 MANE Select	c.-41-5090T>G		intron	N/A	ENSP00000367552.2	Q8NDN9-1
	RCBTB1	ENST00000860932.1		c.-41-5090T>G		intron	N/A	ENSP00000530991.1
	RCBTB1	ENST00000860933.1		c.-21-5110T>G		intron	N/A	ENSP00000530992.1

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

African (AFR) AF: 0.00732 AC: 304 AN: 41558

American (AMR) AF: 0.114 AC: 1741 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0490 AC: 170 AN: 3466

East Asian (EAS) AF: 0.00154 AC: 8 AN: 5186

South Asian (SAS) AF: 0.0367 AC: 177 AN: 4824

European-Finnish (FIN) AF: 0.0288 AC: 306 AN: 10616

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.0307 AC: 2086 AN: 68022

Other (OTH) AF: 0.0227 AC: 48 AN: 2116

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	7.0
DANN	Benign	0.91
PhyloP100		0.11
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: rs7329797; hg19: chr13-50146546;