rs4240711

Positions:

• chr9-134437460-G-A

Variant summary

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

The NM_002957.6(RXRA):​c.*846G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.544 in 152,502 control chromosomes in the GnomAD database, including 24,417 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 0.54 (24301 hom., cov: 33)
  • Exomes 𝑓: 0.65 (116 hom.)
• Consequence: RXRA NM_002957.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.109

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]

RXRA (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• 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	Protein	UniProt
RXRA	NM_002957.6	c.*846G>A		3_prime_UTR_variant	10/10	ENST00000481739.2	NP_002948.1
RXRA	NM_001291920.2	c.*846G>A		3_prime_UTR_variant	10/10		NP_001278849.1
RXRA	NM_001291921.2	c.*846G>A		3_prime_UTR_variant	9/9		NP_001278850.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RXRA	ENST00000481739.2	c.*846G>A		3_prime_UTR_variant	10/10	1	NM_002957.6	ENSP00000419692.1
RXRA	ENST00000356384.4	n.2645G>A		non_coding_transcript_exon_variant	12/12	5

Frequencies

GnomAD3 genomes AF: 0.544 AC: 82569 AN: 151870 Hom.: 24301 Cov.: 33

Gnomad AFR AF: 0.303

Gnomad AMI AF: 0.657

Gnomad AMR AF: 0.579

Gnomad ASJ AF: 0.643

Gnomad EAS AF: 0.657

Gnomad SAS AF: 0.491

Gnomad FIN AF: 0.642

Gnomad MID AF: 0.544

Gnomad NFE AF: 0.655

Gnomad OTH AF: 0.572

GnomAD4 exome AF: 0.652 AC: 335 AN: 514 Hom.: 116 Cov.: 0 AF XY: 0.678 AC XY: 240 AN XY: 354

Gnomad4 AFR exome AF: 0.0833

Gnomad4 ASJ exome AF: 0.500

Gnomad4 EAS exome AF: 0.714

Gnomad4 SAS exome AF: 0.667

Gnomad4 FIN exome AF: 0.614

Gnomad4 NFE exome AF: 0.701

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.543 AC: 82579 AN: 151988 Hom.: 24301 Cov.: 33 AF XY: 0.545 AC XY: 40475 AN XY: 74296

Gnomad4 AFR AF: 0.302

Gnomad4 AMR AF: 0.579

Gnomad4 ASJ AF: 0.643

Gnomad4 EAS AF: 0.657

Gnomad4 SAS AF: 0.489

Gnomad4 FIN AF: 0.642

Gnomad4 NFE AF: 0.655

Gnomad4 OTH AF: 0.566

Alfa AF: 0.590 Hom.: 3542

Bravo AF: 0.531

Asia WGS AF: 0.565 AC: 1967 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.2
DANN	Benign	0.78
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		0.98

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs4240711; hg19: chr9-137329306; COSMIC: COSV62683920;