rs202073736

Variant names:

• chr13-49534180-C-A
• rs202073736
• NM_018191.4:c.1538G>T

Your query was ambiguous. Multiple possible variants found:

• chr13-49534180-C-A
• chr13-49534180-C-G
• chr13-49534180-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_018191.4(RCBTB1):​c.1538G>T​(p.Gly513Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G513A) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RCBTB1 NM_018191.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.16

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.35883477).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RCBTB1	NM_018191.4	c.1538G>T	p.Gly513Val	missense_variant	Exon 13 of 13	ENST00000378302.7	NP_060661.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RCBTB1	ENST00000378302.7	c.1538G>T	p.Gly513Val	missense_variant	Exon 13 of 13	1	NM_018191.4	ENSP00000367552.2
RCBTB1	ENST00000258646.3	c.1538G>T	p.Gly513Val	missense_variant	Exon 11 of 11	2		ENSP00000258646.3
RCBTB1	ENST00000471984.1	n.426G>T		non_coding_transcript_exon_variant	Exon 3 of 3	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.47
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.060
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.025	T;T
Eigen	Uncertain	0.26
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.91	.;D
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.36	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L;L
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	-1.2	N;N
REVEL	Benign	0.27
Sift	Benign	0.12	T;T
Sift4G	Benign	0.078	T;T
Polyphen		0.41	B;B
Vest4		0.55
MutPred		0.47		Gain of catalytic residue at F508 (P = 0);Gain of catalytic residue at F508 (P = 0);
MVP		0.59
MPC		0.24
ClinPred		0.64	D
GERP RS		5.9
Varity_R		0.31
gMVP		0.78

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

Publications

LitVar

Other links and lift over

dbSNP: rs202073736; hg19: chr13-50108316;