rs2076310

Positions:

• chr6-33198257-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021976.5(RXRB):​c.640+51T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.26 in 1,610,972 control chromosomes in the GnomAD database, including 59,525 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.29 (7039 hom., cov: 32)
  • Exomes 𝑓: 0.26 (52486 hom.)
• Consequence: RXRB NM_021976.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.102

Genes affected

RXRB (HGNC:10478): (retinoid X receptor beta) This gene encodes a member of the retinoid X receptor (RXR) family of nuclear receptors which are involved in mediating the effects of retinoic acid (RA). The encoded protein forms homodimers with the retinoic acid, thyroid hormone, and vitamin D receptors, increasing both DNA binding and transcriptional function on their respective response elements. This gene lies within the major histocompatibility complex (MHC) class II region on chromosome 6. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Jul 2012]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.62 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RXRB	NM_021976.5	c.640+51T>C		intron_variant		ENST00000374680.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RXRB	ENST00000374680.4	c.640+51T>C		intron_variant		1	NM_021976.5	P4
RXRB	ENST00000374685.8	c.640+51T>C		intron_variant		1		A1
RXRB	ENST00000483281.5	c.*152+51T>C		intron_variant, NMD_transcript_variant		5
RXRB	ENST00000481441.1	n.328+51T>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.288 AC: 43752 AN: 151954 Hom.: 7012 Cov.: 32

Gnomad AFR AF: 0.365

Gnomad AMI AF: 0.137

Gnomad AMR AF: 0.231

Gnomad ASJ AF: 0.168

Gnomad EAS AF: 0.637

Gnomad SAS AF: 0.303

Gnomad FIN AF: 0.271

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.237

Gnomad OTH AF: 0.297

GnomAD3 exomes AF: 0.275 AC: 67006 AN: 243888 Hom.: 10927 AF XY: 0.274 AC XY: 36488 AN XY: 133248

Gnomad AFR exome AF: 0.365

Gnomad AMR exome AF: 0.191

Gnomad ASJ exome AF: 0.180

Gnomad EAS exome AF: 0.639

Gnomad SAS exome AF: 0.297

Gnomad FIN exome AF: 0.262

Gnomad NFE exome AF: 0.233

Gnomad OTH exome AF: 0.262

GnomAD4 exome AF: 0.257 AC: 374562 AN: 1458900 Hom.: 52486 Cov.: 32 AF XY: 0.257 AC XY: 186444 AN XY: 725866

Gnomad4 AFR exome AF: 0.354

Gnomad4 AMR exome AF: 0.197

Gnomad4 ASJ exome AF: 0.184

Gnomad4 EAS exome AF: 0.647

Gnomad4 SAS exome AF: 0.298

Gnomad4 FIN exome AF: 0.260

Gnomad4 NFE exome AF: 0.240

Gnomad4 OTH exome AF: 0.268

GnomAD4 genome AF: 0.288 AC: 43826 AN: 152072 Hom.: 7039 Cov.: 32 AF XY: 0.290 AC XY: 21548 AN XY: 74338

Gnomad4 AFR AF: 0.365

Gnomad4 AMR AF: 0.231

Gnomad4 ASJ AF: 0.168

Gnomad4 EAS AF: 0.638

Gnomad4 SAS AF: 0.302

Gnomad4 FIN AF: 0.271

Gnomad4 NFE AF: 0.237

Gnomad4 OTH AF: 0.305

Alfa AF: 0.249 Hom.: 9022

Bravo AF: 0.293

Asia WGS AF: 0.390 AC: 1353 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.2
DANN	Benign	0.72

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: rs2076310; hg19: chr6-33166034;