rs12339491

Variant names:

• chr9-134405384-G-A
• rs12339491
• NM_002957.6:c.280-2765G>A

Variant summary

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

The NM_002957.6(RXRA):​c.280-2765G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.102 in 152,288 control chromosomes in the GnomAD database, including 2,586 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 0.10 (2586 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RXRA NM_002957.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0910

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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.344 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RXRA	NM_002957.6	c.280-2765G>A		intron_variant	Intron 2 of 9	ENST00000481739.2	NP_002948.1
RXRA	NM_001291920.2	c.199-2765G>A		intron_variant	Intron 2 of 9		NP_001278849.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RXRA	ENST00000481739.2	c.280-2765G>A		intron_variant	Intron 2 of 9	1	NM_002957.6	ENSP00000419692.1
RXRA	ENST00000672570.1	c.199-2765G>A		intron_variant	Intron 2 of 9			ENSP00000500402.1
RXRA	ENST00000484822.1	n.4205G>A		non_coding_transcript_exon_variant	Exon 3 of 3	2
RXRA	ENST00000356384.4	n.690-2765G>A		intron_variant	Intron 4 of 11	5

Frequencies

GnomAD3 genomes AF: 0.102 AC: 15460 AN: 152170 Hom.: 2573 Cov.: 33

Gnomad AFR AF: 0.349

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0429

Gnomad ASJ AF: 0.00259

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00248

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.00243

Gnomad OTH AF: 0.0742

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 58 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 40

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.102 AC: 15507 AN: 152288 Hom.: 2586 Cov.: 33 AF XY: 0.0984 AC XY: 7327 AN XY: 74458

Gnomad4 AFR AF: 0.349

Gnomad4 AMR AF: 0.0429

Gnomad4 ASJ AF: 0.00259

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00248

Gnomad4 FIN AF: 0.0000941

Gnomad4 NFE AF: 0.00241

Gnomad4 OTH AF: 0.0734

Alfa AF: 0.0628 Hom.: 201

Bravo AF: 0.117

Asia WGS AF: 0.0220 AC: 77 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.4
DANN	Benign	0.64
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs12339491; hg19: chr9-137297230;