13-49534125-G-T

Variant names:

• chr13-49534125-G-T
• rs777487842
• NM_018191.4:c.1593C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_018191.4(RCBTB1):​c.1593C>A​(p.Asn531Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000479 in 1,461,438 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: RCBTB1 NM_018191.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.54
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

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.1593C>A	p.Asn531Lys	missense	Exon 13 of 13	NP_060661.3
	RCBTB1	NM_001352500.2		c.1593C>A	p.Asn531Lys	missense	Exon 13 of 13	NP_001339429.1	Q8NDN9-1
	RCBTB1	NM_001352501.2		c.1593C>A	p.Asn531Lys	missense	Exon 12 of 12	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.1593C>A	p.Asn531Lys	missense	Exon 13 of 13	ENSP00000367552.2	Q8NDN9-1
	RCBTB1	ENST00000258646.3	TSL:2	c.1593C>A	p.Asn531Lys	missense	Exon 11 of 11	ENSP00000258646.3	Q8NDN9-1
	RCBTB1	ENST00000860932.1		c.1593C>A	p.Asn531Lys	missense	Exon 12 of 12	ENSP00000530991.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000479 AC: 7 AN: 1461438 Hom.: 0 Cov.: 33 AF XY: 0.00000550 AC XY: 4 AN XY: 727026

African (AFR) AF: 0.00 AC: 0 AN: 33434

American (AMR) AF: 0.00 AC: 0 AN: 44602

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26112

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86200

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53412

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00000630 AC: 7 AN: 1111842

Other (OTH) AF: 0.00 AC: 0 AN: 60376

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.83
BayesDel_addAF	Benign	-0.048	T
BayesDel_noAF	Benign	-0.31
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.042	T
Eigen	Pathogenic	0.69
Eigen_PC	Pathogenic	0.68
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.030	D
MetaRNN	Uncertain	0.57	D
MetaSVM	Benign	-0.73	T
MutationAssessor	Benign	1.8	L
PhyloP100		6.5
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.15
Sift	Uncertain	0.0030	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.72
MutPred		0.32		Gain of catalytic residue at A528 (P = 0.011)
MVP		0.59
MPC		0.76
ClinPred		0.88	D
GERP RS		5.0
Varity_R		0.33
gMVP		0.37
Mutation Taster		=44/56	disease causing

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: rs777487842; hg19: chr13-50108261; COSMIC: COSV99319718;