rs10548957

Positions:

• chr6-33195860-AAG-A
• chr6-33195860-AAG-AAGAG

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_021976.5(RXRB):​c.1123+45_1123+46del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0534 in 1,610,020 control chromosomes in the GnomAD database, including 4,565 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.10 (1533 hom., cov: 31)
  • Exomes 𝑓: 0.048 (3032 hom.)
• Consequence: RXRB NM_021976.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.19

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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.257 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RXRB	NM_021976.5	c.1123+45_1123+46del		intron_variant		ENST00000374680.4	NP_068811.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RXRB	ENST00000374680.4	c.1123+45_1123+46del		intron_variant		1	NM_021976.5	ENSP00000363812	P4
RXRB	ENST00000374685.8	c.1123+45_1123+46del		intron_variant		1		ENSP00000363817	A1
RXRB	ENST00000481441.1	n.1253_1254del		non_coding_transcript_exon_variant	3/3	2
RXRB	ENST00000483281.5	c.*635+45_*635+46del		intron_variant, NMD_transcript_variant		5		ENSP00000431369

Frequencies

GnomAD3 genomes AF: 0.103 AC: 15616 AN: 151998 Hom.: 1530 Cov.: 31

Gnomad AFR AF: 0.262

Gnomad AMI AF: 0.0208

Gnomad AMR AF: 0.0516

Gnomad ASJ AF: 0.00951

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00228

Gnomad FIN AF: 0.0489

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0478

Gnomad OTH AF: 0.0876

GnomAD3 exomes AF: 0.0454 AC: 11171 AN: 245970 Hom.: 683 AF XY: 0.0397 AC XY: 5328 AN XY: 134082

Gnomad AFR exome AF: 0.275

Gnomad AMR exome AF: 0.0248

Gnomad ASJ exome AF: 0.00937

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00142

Gnomad FIN exome AF: 0.0504

Gnomad NFE exome AF: 0.0431

Gnomad OTH exome AF: 0.0328

GnomAD4 exome AF: 0.0483 AC: 70352 AN: 1457904 Hom.: 3032 AF XY: 0.0458 AC XY: 33228 AN XY: 725008

Gnomad4 AFR exome AF: 0.291

Gnomad4 AMR exome AF: 0.0285

Gnomad4 ASJ exome AF: 0.00874

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00149

Gnomad4 FIN exome AF: 0.0505

Gnomad4 NFE exome AF: 0.0482

Gnomad4 OTH exome AF: 0.0458

GnomAD4 genome AF: 0.103 AC: 15637 AN: 152116 Hom.: 1533 Cov.: 31 AF XY: 0.0985 AC XY: 7330 AN XY: 74406

Gnomad4 AFR AF: 0.262

Gnomad4 AMR AF: 0.0515

Gnomad4 ASJ AF: 0.00951

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00228

Gnomad4 FIN AF: 0.0489

Gnomad4 NFE AF: 0.0478

Gnomad4 OTH AF: 0.0866

Alfa AF: 0.0682 Hom.: 144

Bravo AF: 0.111

Asia WGS AF: 0.0160 AC: 57 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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: rs10548957; hg19: chr6-33163637;