rs2072915

Variant names:

• chr6-33194305-T-A
• rs2072915
• NM_021976.5:c.*377A>T

Your query was ambiguous. Multiple possible variants found:

• chr6-33194305-T-A
• chr6-33194305-T-G

Variant summary

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

The NM_021976.5(RXRB):​c.*377A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.313 in 178,948 control chromosomes in the GnomAD database, including 9,084 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 0.32 (7751 hom., cov: 32)
  • Exomes 𝑓: 0.30 (1333 hom.)
• Consequence: RXRB NM_021976.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.399
• Publications: 34 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=-0.54).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.369 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RXRB	NM_021976.5	MANE Select	c.*377A>T		3_prime_UTR	Exon 10 of 10	NP_068811.1
	RXRB	NM_001270401.2		c.*377A>T		3_prime_UTR	Exon 10 of 10	NP_001257330.1
	RXRB	NM_001291989.2		c.*377A>T		3_prime_UTR	Exon 9 of 9	NP_001278918.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RXRB	ENST00000374680.4	TSL:1 MANE Select	c.*377A>T		3_prime_UTR	Exon 10 of 10	ENSP00000363812.3
	RXRB	ENST00000374685.8	TSL:1	c.*377A>T		3_prime_UTR	Exon 10 of 10	ENSP00000363817.4
	RXRB	ENST00000865272.1		c.*377A>T		3_prime_UTR	Exon 10 of 10	ENSP00000535331.1

Frequencies

GnomAD3 genomes AF: 0.316 AC: 47884 AN: 151692 Hom.: 7748 Cov.: 32

Gnomad AFR AF: 0.361

Gnomad AMI AF: 0.411

Gnomad AMR AF: 0.269

Gnomad ASJ AF: 0.378

Gnomad EAS AF: 0.228

Gnomad SAS AF: 0.384

Gnomad FIN AF: 0.205

Gnomad MID AF: 0.366

Gnomad NFE AF: 0.313

Gnomad OTH AF: 0.323

GnomAD4 exome AF: 0.300 AC: 8141 AN: 27136 Hom.: 1333 Cov.: 0 AF XY: 0.300 AC XY: 4170 AN XY: 13918

African (AFR) AF: 0.361 AC: 320 AN: 886

American (AMR) AF: 0.239 AC: 276 AN: 1154

Ashkenazi Jewish (ASJ) AF: 0.383 AC: 390 AN: 1018

East Asian (EAS) AF: 0.217 AC: 399 AN: 1836

South Asian (SAS) AF: 0.374 AC: 459 AN: 1226

European-Finnish (FIN) AF: 0.221 AC: 210 AN: 950

Middle Eastern (MID) AF: 0.338 AC: 48 AN: 142

European-Non Finnish (NFE) AF: 0.302 AC: 5489 AN: 18148

Other (OTH) AF: 0.310 AC: 550 AN: 1776

GnomAD4 genome AF: 0.316 AC: 47902 AN: 151812 Hom.: 7751 Cov.: 32 AF XY: 0.310 AC XY: 22995 AN XY: 74172

African (AFR) AF: 0.361 AC: 14916 AN: 41370

American (AMR) AF: 0.269 AC: 4109 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.378 AC: 1311 AN: 3468

East Asian (EAS) AF: 0.227 AC: 1164 AN: 5132

South Asian (SAS) AF: 0.384 AC: 1837 AN: 4786

European-Finnish (FIN) AF: 0.205 AC: 2160 AN: 10554

Middle Eastern (MID) AF: 0.367 AC: 108 AN: 294

European-Non Finnish (NFE) AF: 0.313 AC: 21247 AN: 67916

Other (OTH) AF: 0.321 AC: 678 AN: 2110

Alfa AF: 0.319 Hom.: 4543

Bravo AF: 0.318

Asia WGS AF: 0.329 AC: 1146 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	11
DANN	Benign	0.87
PhyloP100		0.40
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs2072915; hg19: chr6-33162082;