6-33198257-A-G

Variant names:

• chr6-33198257-A-G
• rs2076310
• NM_021976.5:c.640+51T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021976.5(RXRB):​c.640+51T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.26 in 1,610,972 control chromosomes in the GnomAD database, including 59,525 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 0.29 (7039 hom., cov: 32)
  • Exomes 𝑓: 0.26 (52486 hom.)
• Consequence: RXRB NM_021976.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.102
• Publications: 42 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 -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 = 0.62 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021976.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RXRB	NM_021976.5	MANE Select	c.640+51T>C		intron	N/A	NP_068811.1
	RXRB	NM_001270401.2		c.640+51T>C		intron	N/A	NP_001257330.1
	RXRB	NM_001291989.2		c.70+51T>C		intron	N/A	NP_001278918.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RXRB	ENST00000374680.4	TSL:1 MANE Select	c.640+51T>C		intron	N/A	ENSP00000363812.3
	RXRB	ENST00000374685.8	TSL:1	c.640+51T>C		intron	N/A	ENSP00000363817.4
	RXRB	ENST00000481441.1	TSL:2	n.328+51T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.288 AC: 43752 AN: 151954 Hom.: 7012 Cov.: 32

Gnomad AFR AF: 0.365

Gnomad AMI AF: 0.137

Gnomad AMR AF: 0.231

Gnomad ASJ AF: 0.168

Gnomad EAS AF: 0.637

Gnomad SAS AF: 0.303

Gnomad FIN AF: 0.271

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.237

Gnomad OTH AF: 0.297

GnomAD2 exomes AF: 0.275 AC: 67006 AN: 243888 AF XY: 0.274

Gnomad AFR exome AF: 0.365

Gnomad AMR exome AF: 0.191

Gnomad ASJ exome AF: 0.180

Gnomad EAS exome AF: 0.639

Gnomad FIN exome AF: 0.262

Gnomad NFE exome AF: 0.233

Gnomad OTH exome AF: 0.262

GnomAD4 exome AF: 0.257 AC: 374562 AN: 1458900 Hom.: 52486 Cov.: 32 AF XY: 0.257 AC XY: 186444 AN XY: 725866

African (AFR) AF: 0.354 AC: 11824 AN: 33442

American (AMR) AF: 0.197 AC: 8813 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.184 AC: 4808 AN: 26122

East Asian (EAS) AF: 0.647 AC: 25663 AN: 39694

South Asian (SAS) AF: 0.298 AC: 25706 AN: 86220

European-Finnish (FIN) AF: 0.260 AC: 13605 AN: 52264

Middle Eastern (MID) AF: 0.252 AC: 1441 AN: 5714

European-Non Finnish (NFE) AF: 0.240 AC: 266552 AN: 1110426

Other (OTH) AF: 0.268 AC: 16150 AN: 60312

GnomAD4 genome AF: 0.288 AC: 43826 AN: 152072 Hom.: 7039 Cov.: 32 AF XY: 0.290 AC XY: 21548 AN XY: 74338

African (AFR) AF: 0.365 AC: 15155 AN: 41470

American (AMR) AF: 0.231 AC: 3525 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.168 AC: 584 AN: 3470

East Asian (EAS) AF: 0.638 AC: 3293 AN: 5162

South Asian (SAS) AF: 0.302 AC: 1455 AN: 4822

European-Finnish (FIN) AF: 0.271 AC: 2866 AN: 10564

Middle Eastern (MID) AF: 0.241 AC: 71 AN: 294

European-Non Finnish (NFE) AF: 0.237 AC: 16108 AN: 67986

Other (OTH) AF: 0.305 AC: 644 AN: 2112

Alfa AF: 0.255 Hom.: 17189

Bravo AF: 0.293

Asia WGS AF: 0.390 AC: 1353 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.2
DANN	Benign	0.72
PhyloP100		0.10
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: rs2076310; hg19: chr6-33166034;