NM_018191.4:c.*6A>G

Variant names:

• chr13-49534116-T-C
• rs7317982
• NM_018191.4:c.*6A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_018191.4(RCBTB1):​c.*6A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.514 in 1,611,914 control chromosomes in the GnomAD database, including 216,382 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.48 (18121 hom., cov: 31)
  • Exomes 𝑓: 0.52 (198261 hom.)
• Consequence: RCBTB1 NM_018191.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -2.46
• Publications: 22 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 13-49534116-T-C is Benign according to our data. Variant chr13-49534116-T-C is described in ClinVar as Benign. ClinVar VariationId is 1265543.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.529 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.*6A>G		3_prime_UTR	Exon 13 of 13	NP_060661.3
	RCBTB1	NM_001352500.2		c.*6A>G		3_prime_UTR	Exon 13 of 13	NP_001339429.1	Q8NDN9-1
	RCBTB1	NM_001352501.2		c.*6A>G		3_prime_UTR	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.*6A>G		3_prime_UTR	Exon 13 of 13	ENSP00000367552.2	Q8NDN9-1
	RCBTB1	ENST00000258646.3	TSL:2	c.*6A>G		3_prime_UTR	Exon 11 of 11	ENSP00000258646.3	Q8NDN9-1
	RCBTB1	ENST00000860932.1		c.*6A>G		3_prime_UTR	Exon 12 of 12	ENSP00000530991.1

Frequencies

GnomAD3 genomes AF: 0.484 AC: 73463 AN: 151816 Hom.: 18107 Cov.: 31

Gnomad AFR AF: 0.390

Gnomad AMI AF: 0.434

Gnomad AMR AF: 0.527

Gnomad ASJ AF: 0.545

Gnomad EAS AF: 0.472

Gnomad SAS AF: 0.321

Gnomad FIN AF: 0.529

Gnomad MID AF: 0.601

Gnomad NFE AF: 0.533

Gnomad OTH AF: 0.512

GnomAD2 exomes AF: 0.495 AC: 123937 AN: 250412 AF XY: 0.488

Gnomad AFR exome AF: 0.384

Gnomad AMR exome AF: 0.532

Gnomad ASJ exome AF: 0.566

Gnomad EAS exome AF: 0.479

Gnomad FIN exome AF: 0.539

Gnomad NFE exome AF: 0.534

Gnomad OTH exome AF: 0.527

GnomAD4 exome AF: 0.517 AC: 755158 AN: 1459980 Hom.: 198261 Cov.: 37 AF XY: 0.513 AC XY: 372360 AN XY: 726286

African (AFR) AF: 0.386 AC: 12893 AN: 33410

American (AMR) AF: 0.529 AC: 23500 AN: 44464

Ashkenazi Jewish (ASJ) AF: 0.569 AC: 14817 AN: 26052

East Asian (EAS) AF: 0.495 AC: 19613 AN: 39656

South Asian (SAS) AF: 0.318 AC: 27365 AN: 86094

European-Finnish (FIN) AF: 0.535 AC: 28549 AN: 53342

Middle Eastern (MID) AF: 0.542 AC: 3124 AN: 5766

European-Non Finnish (NFE) AF: 0.535 AC: 594281 AN: 1110878

Other (OTH) AF: 0.514 AC: 31016 AN: 60318

GnomAD4 genome AF: 0.484 AC: 73513 AN: 151934 Hom.: 18121 Cov.: 31 AF XY: 0.480 AC XY: 35652 AN XY: 74244

African (AFR) AF: 0.390 AC: 16136 AN: 41420

American (AMR) AF: 0.527 AC: 8048 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.545 AC: 1890 AN: 3466

East Asian (EAS) AF: 0.473 AC: 2440 AN: 5164

South Asian (SAS) AF: 0.321 AC: 1545 AN: 4818

European-Finnish (FIN) AF: 0.529 AC: 5577 AN: 10550

Middle Eastern (MID) AF: 0.599 AC: 176 AN: 294

European-Non Finnish (NFE) AF: 0.533 AC: 36235 AN: 67948

Other (OTH) AF: 0.510 AC: 1071 AN: 2102

Alfa AF: 0.521 Hom.: 32658

Bravo AF: 0.485

Asia WGS AF: 0.393 AC: 1364 AN: 3478

EpiCase AF: 0.539

EpiControl AF: 0.534

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	RCBTB1-related retinopathy (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.22
DANN	Benign	0.53
PhyloP100		-2.5
Mutation Taster		=100/0	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: rs7317982; hg19: chr13-50108252; COSMIC: COSV51633681;