rs2274278

Variant names:

• chr13-49552246-G-A
• rs2274278
• NM_018191.4:c.643C>T

Your query was ambiguous. Multiple possible variants found:

• chr13-49552246-G-A
• chr13-49552246-G-T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_018191.4(RCBTB1):​c.643C>T​(p.Leu215Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.846 in 1,601,994 control chromosomes in the GnomAD database, including 573,484 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.85 (55192 hom., cov: 30)
  • Exomes 𝑓: 0.84 (518292 hom.)
• Consequence: RCBTB1 NM_018191.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.881
• Publications: 23 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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BP6: Variant 13-49552246-G-A is Benign according to our data. Variant chr13-49552246-G-A is described in ClinVar as Benign. ClinVar VariationId is 1170496.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.881 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.881 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.643C>T	p.Leu215Leu	synonymous	Exon 7 of 13	NP_060661.3
	RCBTB1	NM_001352500.2		c.643C>T	p.Leu215Leu	synonymous	Exon 7 of 13	NP_001339429.1	Q8NDN9-1
	RCBTB1	NM_001352501.2		c.643C>T	p.Leu215Leu	synonymous	Exon 6 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.643C>T	p.Leu215Leu	synonymous	Exon 7 of 13	ENSP00000367552.2	Q8NDN9-1
	RCBTB1	ENST00000258646.3	TSL:2	c.643C>T	p.Leu215Leu	synonymous	Exon 5 of 11	ENSP00000258646.3	Q8NDN9-1
	RCBTB1	ENST00000860932.1		c.643C>T	p.Leu215Leu	synonymous	Exon 6 of 12	ENSP00000530991.1

Frequencies

GnomAD3 genomes AF: 0.851 AC: 129286 AN: 151976 Hom.: 55125 Cov.: 30

Gnomad AFR AF: 0.888

Gnomad AMI AF: 0.648

Gnomad AMR AF: 0.865

Gnomad ASJ AF: 0.796

Gnomad EAS AF: 0.895

Gnomad SAS AF: 0.827

Gnomad FIN AF: 0.798

Gnomad MID AF: 0.807

Gnomad NFE AF: 0.837

Gnomad OTH AF: 0.832

GnomAD2 exomes AF: 0.847 AC: 197908 AN: 233604 AF XY: 0.842

Gnomad AFR exome AF: 0.893

Gnomad AMR exome AF: 0.904

Gnomad ASJ exome AF: 0.815

Gnomad EAS exome AF: 0.893

Gnomad FIN exome AF: 0.808

Gnomad NFE exome AF: 0.835

Gnomad OTH exome AF: 0.829

GnomAD4 exome AF: 0.845 AC: 1225152 AN: 1449900 Hom.: 518292 Cov.: 40 AF XY: 0.843 AC XY: 607215 AN XY: 720072

African (AFR) AF: 0.884 AC: 29477 AN: 33356

American (AMR) AF: 0.899 AC: 38979 AN: 43338

Ashkenazi Jewish (ASJ) AF: 0.817 AC: 21072 AN: 25802

East Asian (EAS) AF: 0.884 AC: 34948 AN: 39544

South Asian (SAS) AF: 0.815 AC: 68593 AN: 84138

European-Finnish (FIN) AF: 0.811 AC: 42590 AN: 52524

Middle Eastern (MID) AF: 0.804 AC: 4520 AN: 5624

European-Non Finnish (NFE) AF: 0.845 AC: 934185 AN: 1105636

Other (OTH) AF: 0.847 AC: 50788 AN: 59938

GnomAD4 genome AF: 0.851 AC: 129413 AN: 152094 Hom.: 55192 Cov.: 30 AF XY: 0.848 AC XY: 63060 AN XY: 74334

African (AFR) AF: 0.888 AC: 36877 AN: 41518

American (AMR) AF: 0.865 AC: 13207 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.796 AC: 2764 AN: 3472

East Asian (EAS) AF: 0.895 AC: 4629 AN: 5170

South Asian (SAS) AF: 0.828 AC: 3991 AN: 4818

European-Finnish (FIN) AF: 0.798 AC: 8424 AN: 10550

Middle Eastern (MID) AF: 0.803 AC: 236 AN: 294

European-Non Finnish (NFE) AF: 0.837 AC: 56933 AN: 67986

Other (OTH) AF: 0.833 AC: 1762 AN: 2114

Alfa AF: 0.846 Hom.: 28188

Bravo AF: 0.858

Asia WGS AF: 0.862 AC: 2998 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	RCBTB1-related retinopathy (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	7.7
DANN	Benign	0.74
PhyloP100		0.88
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=96/4	polymorphism (auto)

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: rs2274278; hg19: chr13-50126382; COSMIC: COSV108050804;