6-33194451-A-T

Variant names:

• chr6-33194451-A-T
• rs5030979
• NM_021976.5:c.*231T>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
RXRB	NM_021976.5	c.*231T>A		3_prime_UTR_variant	Exon 10 of 10	ENST00000374680.4	NP_068811.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RXRB	ENST00000374680.4	c.*231T>A		3_prime_UTR_variant	Exon 10 of 10	1	NM_021976.5	ENSP00000363812.3

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

African (AFR) AF: 0.0203 AC: 209 AN: 10298

American (AMR) AF: 0.280 AC: 3558 AN: 12696

Ashkenazi Jewish (ASJ) AF: 0.0874 AC: 1017 AN: 11630

East Asian (EAS) AF: 0.0669 AC: 1791 AN: 26786

South Asian (SAS) AF: 0.0708 AC: 1700 AN: 24018

European-Finnish (FIN) AF: 0.197 AC: 4984 AN: 25362

Middle Eastern (MID) AF: 0.139 AC: 232 AN: 1670

European-Non Finnish (NFE) AF: 0.124 AC: 27233 AN: 220170

Other (OTH) AF: 0.112 AC: 2446 AN: 21820

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

African (AFR) AF: 0.0217 AC: 901 AN: 41586

American (AMR) AF: 0.230 AC: 3519 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0781 AC: 271 AN: 3472

East Asian (EAS) AF: 0.0333 AC: 173 AN: 5194

South Asian (SAS) AF: 0.0739 AC: 357 AN: 4830

European-Finnish (FIN) AF: 0.210 AC: 2228 AN: 10606

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.125 AC: 8502 AN: 68006

Other (OTH) AF: 0.0938 AC: 198 AN: 2110

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
PhyloP100		0.14
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs5030979; hg19: chr6-33162228;