6-33194451-A-T

Position:

• chr6-33194451-A-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_021976.5(RXRB):​c.*231T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.117 in 506,762 control chromosomes in the GnomAD database, including 4,392 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 0.11 (1320 hom., cov: 32)
  • Exomes 𝑓: 0.12 (3072 hom.)
• Consequence: RXRB NM_021976.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.141

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.28).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.224 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RXRB	NM_021976.5	c.*231T>A		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.*231T>A		3_prime_UTR_variant	10/10	1	NM_021976.5	ENSP00000363812.3
RXRB	ENST00000374685.8	c.*231T>A		3_prime_UTR_variant	10/10	1		ENSP00000363817.4
RXRB	ENST00000483281.5	n.*1345T>A		non_coding_transcript_exon_variant	9/9	5		ENSP00000431369.1
RXRB	ENST00000483281.5	n.*1345T>A		3_prime_UTR_variant	9/9	5		ENSP00000431369.1

Frequencies

GnomAD3 genomes AF: 0.107 AC: 16232 AN: 152194 Hom.: 1316 Cov.: 32

Gnomad AFR AF: 0.0217

Gnomad AMI AF: 0.0724

Gnomad AMR AF: 0.230

Gnomad ASJ AF: 0.0781

Gnomad EAS AF: 0.0327

Gnomad SAS AF: 0.0720

Gnomad FIN AF: 0.210

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.125

Gnomad OTH AF: 0.0958

GnomAD4 exome AF: 0.122 AC: 43170 AN: 354450 Hom.: 3072 Cov.: 4 AF XY: 0.120 AC XY: 22067 AN XY: 183450

Gnomad4 AFR exome AF: 0.0203

Gnomad4 AMR exome AF: 0.280

Gnomad4 ASJ exome AF: 0.0874

Gnomad4 EAS exome AF: 0.0669

Gnomad4 SAS exome AF: 0.0708

Gnomad4 FIN exome AF: 0.197

Gnomad4 NFE exome AF: 0.124

Gnomad4 OTH exome AF: 0.112

GnomAD4 genome AF: 0.107 AC: 16244 AN: 152312 Hom.: 1320 Cov.: 32 AF XY: 0.111 AC XY: 8286 AN XY: 74480

Gnomad4 AFR AF: 0.0217

Gnomad4 AMR AF: 0.230

Gnomad4 ASJ AF: 0.0781

Gnomad4 EAS AF: 0.0333

Gnomad4 SAS AF: 0.0739

Gnomad4 FIN AF: 0.210

Gnomad4 NFE AF: 0.125

Gnomad4 OTH AF: 0.0938

Alfa AF: 0.114 Hom.: 165

Bravo AF: 0.108

Asia WGS AF: 0.0480 AC: 168 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.28
CADD	Benign	9.6
DANN	Benign	0.77

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: rs5030979; hg19: chr6-33162228;