rs16659

Variant names:

• chr13-49533070-AAAAGTGAAAGATGAT-A
• rs16659
• NM_018191.4:c.*1037_*1051delATCATCTTTCACTTT

Your query was ambiguous. Multiple possible variants found:

• chr13-49533070-AAAAGTGAAAGATGAT-A
• chr13-49533070-AAAAGTGAAAGATGAT-AAAAGTGAAAGATGATAAAGTGAAAGATGAT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_018191.4(RCBTB1):​c.*1037_*1051delATCATCTTTCACTTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.47 (17528 hom., cov: 0)
  • Failed GnomAD Quality Control
• Consequence: RCBTB1 NM_018191.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.62
• Publications: 4 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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.527 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.*1037_*1051delATCATCTTTCACTTT		3_prime_UTR	Exon 13 of 13	NP_060661.3
	RCBTB1	NM_001352500.2		c.*1037_*1051delATCATCTTTCACTTT		3_prime_UTR	Exon 13 of 13	NP_001339429.1	Q8NDN9-1
	RCBTB1	NM_001352501.2		c.*1037_*1051delATCATCTTTCACTTT		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.*1037_*1051delATCATCTTTCACTTT		3_prime_UTR	Exon 13 of 13	ENSP00000367552.2	Q8NDN9-1
	RCBTB1	ENST00000258646.3	TSL:2	c.*1037_*1051delATCATCTTTCACTTT		3_prime_UTR	Exon 11 of 11	ENSP00000258646.3	Q8NDN9-1
	RCBTB1	ENST00000860932.1		c.*1037_*1051delATCATCTTTCACTTT		3_prime_UTR	Exon 12 of 12	ENSP00000530991.1

Frequencies

GnomAD3 genomes AF: 0.475 AC: 72012 AN: 151596 Hom.: 17516 Cov.: 0

Gnomad AFR AF: 0.364

Gnomad AMI AF: 0.432

Gnomad AMR AF: 0.519

Gnomad ASJ AF: 0.541

Gnomad EAS AF: 0.469

Gnomad SAS AF: 0.321

Gnomad FIN AF: 0.526

Gnomad MID AF: 0.598

Gnomad NFE AF: 0.532

Gnomad OTH AF: 0.503

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.475 AC: 72061 AN: 151716 Hom.: 17528 Cov.: 0 AF XY: 0.471 AC XY: 34953 AN XY: 74138

African (AFR) AF: 0.364 AC: 15069 AN: 41384

American (AMR) AF: 0.520 AC: 7912 AN: 15224

Ashkenazi Jewish (ASJ) AF: 0.541 AC: 1876 AN: 3468

East Asian (EAS) AF: 0.470 AC: 2431 AN: 5170

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

European-Finnish (FIN) AF: 0.526 AC: 5529 AN: 10514

Middle Eastern (MID) AF: 0.595 AC: 175 AN: 294

European-Non Finnish (NFE) AF: 0.532 AC: 36080 AN: 67834

Other (OTH) AF: 0.500 AC: 1051 AN: 2100

Alfa AF: 0.497 Hom.: 2035

Bravo AF: 0.476

Asia WGS AF: 0.390 AC: 1352 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.6
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: rs16659; hg19: chr13-50107206; COSMIC: COSV51633630; COSMIC: COSV51633630;