rs2744537

Variant names:

• chr6-33194438-A-C
• rs2744537
• NM_021976.5:c.*244T>G

Your query was ambiguous. Multiple possible variants found:

• chr6-33194438-A-C
• chr6-33194438-A-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.*244T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.769 in 492,318 control chromosomes in the GnomAD database, including 147,615 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 0.78 (47204 hom., cov: 33)
  • Exomes 𝑓: 0.76 (100411 hom.)
• Consequence: RXRB NM_021976.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0500
• Publications: 27 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 = 0.95 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.*244T>G		3_prime_UTR	Exon 10 of 10	NP_068811.1	Q5STP9
	RXRB	NM_001270401.2		c.*244T>G		3_prime_UTR	Exon 10 of 10	NP_001257330.1	A0A0S2Z570
	RXRB	NM_001291989.2		c.*244T>G		3_prime_UTR	Exon 9 of 9	NP_001278918.1	A0A0G2JKR7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RXRB	ENST00000374680.4	TSL:1 MANE Select	c.*244T>G		3_prime_UTR	Exon 10 of 10	ENSP00000363812.3	P28702-1
	RXRB	ENST00000374685.8	TSL:1	c.*244T>G		3_prime_UTR	Exon 10 of 10	ENSP00000363817.4	P28702-3
	RXRB	ENST00000865272.1		c.*244T>G		3_prime_UTR	Exon 10 of 10	ENSP00000535331.1

Frequencies

GnomAD3 genomes AF: 0.783 AC: 119105 AN: 152116 Hom.: 47160 Cov.: 33

Gnomad AFR AF: 0.871

Gnomad AMI AF: 0.620

Gnomad AMR AF: 0.787

Gnomad ASJ AF: 0.801

Gnomad EAS AF: 0.972

Gnomad SAS AF: 0.905

Gnomad FIN AF: 0.708

Gnomad MID AF: 0.816

Gnomad NFE AF: 0.718

Gnomad OTH AF: 0.799

GnomAD4 exome AF: 0.762 AC: 259196 AN: 340084 Hom.: 100411 Cov.: 3 AF XY: 0.766 AC XY: 134603 AN XY: 175682

African (AFR) AF: 0.872 AC: 8480 AN: 9730

American (AMR) AF: 0.800 AC: 9841 AN: 12306

Ashkenazi Jewish (ASJ) AF: 0.807 AC: 9128 AN: 11318

East Asian (EAS) AF: 0.986 AC: 25358 AN: 25722

South Asian (SAS) AF: 0.886 AC: 19985 AN: 22566

European-Finnish (FIN) AF: 0.703 AC: 17282 AN: 24572

Middle Eastern (MID) AF: 0.838 AC: 1347 AN: 1608

European-Non Finnish (NFE) AF: 0.718 AC: 151565 AN: 211114

Other (OTH) AF: 0.767 AC: 16210 AN: 21148

GnomAD4 genome AF: 0.783 AC: 119205 AN: 152234 Hom.: 47204 Cov.: 33 AF XY: 0.784 AC XY: 58373 AN XY: 74434

African (AFR) AF: 0.871 AC: 36194 AN: 41554

American (AMR) AF: 0.786 AC: 12032 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.801 AC: 2781 AN: 3472

East Asian (EAS) AF: 0.972 AC: 5040 AN: 5184

South Asian (SAS) AF: 0.905 AC: 4358 AN: 4816

European-Finnish (FIN) AF: 0.708 AC: 7497 AN: 10594

Middle Eastern (MID) AF: 0.823 AC: 242 AN: 294

European-Non Finnish (NFE) AF: 0.718 AC: 48802 AN: 67994

Other (OTH) AF: 0.801 AC: 1694 AN: 2114

Alfa AF: 0.754 Hom.: 53793

Bravo AF: 0.793

Asia WGS AF: 0.901 AC: 3130 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	11
DANN	Benign	0.60
PhyloP100		0.050
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: rs2744537; hg19: chr6-33162215;