rs2072915

chr6-33194305-T-Achr6-33194305-T-G

Variant summary

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

The NM_021976.5(RXRB):c.*377A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.313 in 178,948 control chromosomes in the GnomAD database, including 9,084 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 0.32 (7751 hom., cov: 32)
  • Exomes 𝑓: 0.30 (1333 hom.)
• Consequence: RXRB NM_021976.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.399

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=-0.54).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.369 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RXRB	NM_021976.5	c.*377A>T		3_prime_UTR_variant	10/10	ENST00000374680.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RXRB	ENST00000374680.4	c.*377A>T		3_prime_UTR_variant	10/10	1	NM_021976.5	P4
RXRB	ENST00000374685.8	c.*377A>T		3_prime_UTR_variant	10/10	1		A1
RXRB	ENST00000483281.5	c.*1491A>T		3_prime_UTR_variant, NMD_transcript_variant	9/9	5

Frequencies

GnomAD3 genomes AF: 0.316 AC: 47884 AN: 151692 Hom.: 7748 Cov.: 32

Gnomad AFR AF: 0.361

Gnomad AMI AF: 0.411

Gnomad AMR AF: 0.269

Gnomad ASJ AF: 0.378

Gnomad EAS AF: 0.228

Gnomad SAS AF: 0.384

Gnomad FIN AF: 0.205

Gnomad MID AF: 0.366

Gnomad NFE AF: 0.313

Gnomad OTH AF: 0.323

GnomAD4 exome AF: 0.300 AC: 8141 AN: 27136 Hom.: 1333 Cov.: 0 AF XY: 0.300 AC XY: 4170 AN XY: 13918

Gnomad4 AFR exome AF: 0.361

Gnomad4 AMR exome AF: 0.239

Gnomad4 ASJ exome AF: 0.383

Gnomad4 EAS exome AF: 0.217

Gnomad4 SAS exome AF: 0.374

Gnomad4 FIN exome AF: 0.221

Gnomad4 NFE exome AF: 0.302

Gnomad4 OTH exome AF: 0.310

GnomAD4 genome AF: 0.316 AC: 47902 AN: 151812 Hom.: 7751 Cov.: 32 AF XY: 0.310 AC XY: 22995 AN XY: 74172

Gnomad4 AFR AF: 0.361

Gnomad4 AMR AF: 0.269

Gnomad4 ASJ AF: 0.378

Gnomad4 EAS AF: 0.227

Gnomad4 SAS AF: 0.384

Gnomad4 FIN AF: 0.205

Gnomad4 NFE AF: 0.313

Gnomad4 OTH AF: 0.321

Alfa AF: 0.319 Hom.: 4543

Bravo AF: 0.318

Asia WGS AF: 0.329 AC: 1146 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
Cadd	Benign	11
Dann	Benign	0.87
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs2072915; hg19: chr6-33162082;