rs2234753

Positions:

• chr9-134401915-G-A
• chr9-134401915-G-T

Variant summary

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

The NM_002957.6(RXRA):​c.279+33G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.765 in 1,515,030 control chromosomes in the GnomAD database, including 445,516 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 0.80 (48457 hom., cov: 31)
  • Exomes 𝑓: 0.76 (397059 hom.)
• Consequence: RXRA NM_002957.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.334

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.903 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RXRA	NM_002957.6	c.279+33G>A		intron_variant		ENST00000481739.2
RXRA	NM_001291920.2	c.198+33G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RXRA	ENST00000481739.2	c.279+33G>A		intron_variant		1	NM_002957.6	P3

Frequencies

GnomAD3 genomes AF: 0.795 AC: 120769 AN: 151882 Hom.: 48415 Cov.: 31

Gnomad AFR AF: 0.911

Gnomad AMI AF: 0.874

Gnomad AMR AF: 0.710

Gnomad ASJ AF: 0.697

Gnomad EAS AF: 0.774

Gnomad SAS AF: 0.627

Gnomad FIN AF: 0.780

Gnomad MID AF: 0.668

Gnomad NFE AF: 0.765

Gnomad OTH AF: 0.776

GnomAD3 exomes AF: 0.773 AC: 140973 AN: 182344 Hom.: 54304 AF XY: 0.768 AC XY: 76892 AN XY: 100130

Gnomad AFR exome AF: 0.929

Gnomad AMR exome AF: 0.699

Gnomad ASJ exome AF: 0.729

Gnomad EAS exome AF: 0.806

Gnomad SAS exome AF: 0.659

Gnomad FIN exome AF: 0.795

Gnomad NFE exome AF: 0.799

Gnomad OTH exome AF: 0.762

GnomAD4 exome AF: 0.761 AC: 1037849 AN: 1363032 Hom.: 397059 Cov.: 24 AF XY: 0.757 AC XY: 509389 AN XY: 673320

Gnomad4 AFR exome AF: 0.923

Gnomad4 AMR exome AF: 0.692

Gnomad4 ASJ exome AF: 0.708

Gnomad4 EAS exome AF: 0.759

Gnomad4 SAS exome AF: 0.626

Gnomad4 FIN exome AF: 0.775

Gnomad4 NFE exome AF: 0.770

Gnomad4 OTH exome AF: 0.754

GnomAD4 genome AF: 0.795 AC: 120864 AN: 151998 Hom.: 48457 Cov.: 31 AF XY: 0.792 AC XY: 58802 AN XY: 74286

Gnomad4 AFR AF: 0.911

Gnomad4 AMR AF: 0.710

Gnomad4 ASJ AF: 0.697

Gnomad4 EAS AF: 0.774

Gnomad4 SAS AF: 0.626

Gnomad4 FIN AF: 0.780

Gnomad4 NFE AF: 0.765

Gnomad4 OTH AF: 0.770

Alfa AF: 0.769 Hom.: 8170

Bravo AF: 0.798

Asia WGS AF: 0.705 AC: 2446 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.5
DANN	Benign	0.34
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.0

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: rs2234753; hg19: chr9-137293761;