rs1805343

Positions:

• chr9-134436440-G-A
• chr9-134436440-G-C

Variant summary

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

The NM_002957.6(RXRA):​c.1242-27G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.624 in 1,610,376 control chromosomes in the GnomAD database, including 320,972 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 0.53 (23813 hom., cov: 35)
  • Exomes 𝑓: 0.63 (297159 hom.)
• Consequence: RXRA NM_002957.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.85

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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.65 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RXRA	NM_002957.6	c.1242-27G>A		intron_variant		ENST00000481739.2
RXRA	NM_001291920.2	c.1161-27G>A		intron_variant
RXRA	NM_001291921.2	c.951-27G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RXRA	ENST00000481739.2	c.1242-27G>A		intron_variant		1	NM_002957.6	P3
RXRA	ENST00000672570.1	c.1161-27G>A		intron_variant				A1
RXRA	ENST00000356384.4	n.1652-27G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.531 AC: 80778 AN: 152088 Hom.: 23816 Cov.: 35

Gnomad AFR AF: 0.260

Gnomad AMI AF: 0.653

Gnomad AMR AF: 0.574

Gnomad ASJ AF: 0.636

Gnomad EAS AF: 0.658

Gnomad SAS AF: 0.491

Gnomad FIN AF: 0.642

Gnomad MID AF: 0.544

Gnomad NFE AF: 0.655

Gnomad OTH AF: 0.562

GnomAD3 exomes AF: 0.593 AC: 147282 AN: 248256 Hom.: 45132 AF XY: 0.595 AC XY: 80019 AN XY: 134478

Gnomad AFR exome AF: 0.251

Gnomad AMR exome AF: 0.580

Gnomad ASJ exome AF: 0.664

Gnomad EAS exome AF: 0.648

Gnomad SAS exome AF: 0.487

Gnomad FIN exome AF: 0.647

Gnomad NFE exome AF: 0.650

Gnomad OTH exome AF: 0.606

GnomAD4 exome AF: 0.634 AC: 924124 AN: 1458168 Hom.: 297159 Cov.: 39 AF XY: 0.630 AC XY: 457062 AN XY: 725518

Gnomad4 AFR exome AF: 0.250

Gnomad4 AMR exome AF: 0.577

Gnomad4 ASJ exome AF: 0.666

Gnomad4 EAS exome AF: 0.658

Gnomad4 SAS exome AF: 0.486

Gnomad4 FIN exome AF: 0.648

Gnomad4 NFE exome AF: 0.658

Gnomad4 OTH exome AF: 0.616

GnomAD4 genome AF: 0.531 AC: 80776 AN: 152208 Hom.: 23813 Cov.: 35 AF XY: 0.533 AC XY: 39676 AN XY: 74412

Gnomad4 AFR AF: 0.259

Gnomad4 AMR AF: 0.574

Gnomad4 ASJ AF: 0.636

Gnomad4 EAS AF: 0.658

Gnomad4 SAS AF: 0.489

Gnomad4 FIN AF: 0.642

Gnomad4 NFE AF: 0.655

Gnomad4 OTH AF: 0.556

Alfa AF: 0.632 Hom.: 49204

Bravo AF: 0.516

Asia WGS AF: 0.560 AC: 1951 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.051
DANN	Benign	0.62

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs1805343; hg19: chr9-137328286; COSMIC: COSV62683543;