rs1536475

Positions:

• chr9-134429310-A-G
• chr9-134429310-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000481739.2(RXRA):​c.1043+70A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.815 in 1,529,316 control chromosomes in the GnomAD database, including 510,233 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 0.85 (55629 hom., cov: 34)
  • Exomes 𝑓: 0.81 (454604 hom.)
• Consequence: RXRA ENST00000481739.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.89

Genes affected

RXRA (HGNC:10477): (retinoid X receptor alpha) Retinoid X receptors (RXRs) and retinoic acid receptors (RARs) are nuclear receptors that mediate the biological effects of retinoids by their involvement in retinoic acid-mediated gene activation. These receptors function as transcription factors by binding as homodimers or heterodimers to specific sequences in the promoters of target genes. The protein encoded by this gene is a member of the steroid and thyroid hormone receptor superfamily of transcriptional regulators. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, May 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.952 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RXRA	NM_002957.6	c.1043+70A>G		intron_variant		ENST00000481739.2	NP_002948.1
RXRA	NM_001291920.2	c.962+70A>G		intron_variant			NP_001278849.1
RXRA	NM_001291921.2	c.752+70A>G		intron_variant			NP_001278850.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RXRA	ENST00000481739.2	c.1043+70A>G		intron_variant		1	NM_002957.6	ENSP00000419692	P3
RXRA	ENST00000672570.1	c.962+70A>G		intron_variant				ENSP00000500402	A1
RXRA	ENST00000356384.4	n.1453+70A>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.851 AC: 129517 AN: 152140 Hom.: 55572 Cov.: 34

Gnomad AFR AF: 0.960

Gnomad AMI AF: 0.910

Gnomad AMR AF: 0.804

Gnomad ASJ AF: 0.766

Gnomad EAS AF: 0.758

Gnomad SAS AF: 0.684

Gnomad FIN AF: 0.853

Gnomad MID AF: 0.693

Gnomad NFE AF: 0.820

Gnomad OTH AF: 0.819

GnomAD4 exome AF: 0.811 AC: 1116858 AN: 1377058 Hom.: 454604 AF XY: 0.806 AC XY: 551492 AN XY: 684540

Gnomad4 AFR exome AF: 0.966

Gnomad4 AMR exome AF: 0.755

Gnomad4 ASJ exome AF: 0.785

Gnomad4 EAS exome AF: 0.745

Gnomad4 SAS exome AF: 0.670

Gnomad4 FIN exome AF: 0.839

Gnomad4 NFE exome AF: 0.822

Gnomad4 OTH exome AF: 0.807

GnomAD4 genome AF: 0.851 AC: 129629 AN: 152258 Hom.: 55629 Cov.: 34 AF XY: 0.849 AC XY: 63246 AN XY: 74452

Gnomad4 AFR AF: 0.960

Gnomad4 AMR AF: 0.804

Gnomad4 ASJ AF: 0.766

Gnomad4 EAS AF: 0.758

Gnomad4 SAS AF: 0.683

Gnomad4 FIN AF: 0.853

Gnomad4 NFE AF: 0.820

Gnomad4 OTH AF: 0.815

Alfa AF: 0.817 Hom.: 47052

Bravo AF: 0.853

Asia WGS AF: 0.732 AC: 2549 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.087
DANN	Benign	0.33
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs1536475; hg19: chr9-137321156; COSMIC: COSV62683908;