rs2744537

Positions:

• chr6-33194438-A-C
• chr6-33194438-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.*244T>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 0.769 in 492,318 control chromosomes in the GnomAD database, including 147,615 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 0.78 (47204 hom., cov: 33)
  • Exomes 𝑓: 0.76 (100411 hom.)
• Consequence: RXRB NM_021976.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0500

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 = 0.95 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RXRB	NM_021976.5	c.*244T>G		3_prime_UTR_variant	10/10	ENST00000374680.4	NP_068811.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RXRB	ENST00000374680.4	c.*244T>G		3_prime_UTR_variant	10/10	1	NM_021976.5	ENSP00000363812	P4
RXRB	ENST00000374685.8	c.*244T>G		3_prime_UTR_variant	10/10	1		ENSP00000363817	A1
RXRB	ENST00000483281.5	c.*1358T>G		3_prime_UTR_variant, NMD_transcript_variant	9/9	5		ENSP00000431369

Frequencies

GnomAD3 genomes AF: 0.783 AC: 119105 AN: 152116 Hom.: 47160 Cov.: 33

Gnomad AFR AF: 0.871

Gnomad AMI AF: 0.620

Gnomad AMR AF: 0.787

Gnomad ASJ AF: 0.801

Gnomad EAS AF: 0.972

Gnomad SAS AF: 0.905

Gnomad FIN AF: 0.708

Gnomad MID AF: 0.816

Gnomad NFE AF: 0.718

Gnomad OTH AF: 0.799

GnomAD4 exome AF: 0.762 AC: 259196 AN: 340084 Hom.: 100411 Cov.: 3 AF XY: 0.766 AC XY: 134603 AN XY: 175682

Gnomad4 AFR exome AF: 0.872

Gnomad4 AMR exome AF: 0.800

Gnomad4 ASJ exome AF: 0.807

Gnomad4 EAS exome AF: 0.986

Gnomad4 SAS exome AF: 0.886

Gnomad4 FIN exome AF: 0.703

Gnomad4 NFE exome AF: 0.718

Gnomad4 OTH exome AF: 0.767

GnomAD4 genome AF: 0.783 AC: 119205 AN: 152234 Hom.: 47204 Cov.: 33 AF XY: 0.784 AC XY: 58373 AN XY: 74434

Gnomad4 AFR AF: 0.871

Gnomad4 AMR AF: 0.786

Gnomad4 ASJ AF: 0.801

Gnomad4 EAS AF: 0.972

Gnomad4 SAS AF: 0.905

Gnomad4 FIN AF: 0.708

Gnomad4 NFE AF: 0.718

Gnomad4 OTH AF: 0.801

Alfa AF: 0.743 Hom.: 32199

Bravo AF: 0.793

Asia WGS AF: 0.901 AC: 3130 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	11
DANN	Benign	0.60

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: rs2744537; hg19: chr6-33162215;