NM_002957.6:c.279+33G>A

Variant names:

• chr9-134401915-G-A
• rs2234753
• NM_002957.6:c.279+33G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 10 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
RXRA	NM_002957.6	c.279+33G>A		intron_variant	Intron 2 of 9	ENST00000481739.2	NP_002948.1
RXRA	NM_001291920.2	c.198+33G>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.279+33G>A		intron_variant	Intron 2 of 9	1	NM_002957.6	ENSP00000419692.1

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

GnomAD2 exomes AF: 0.773 AC: 140973 AN: 182344 AF XY: 0.768

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 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

African (AFR) AF: 0.923 AC: 28699 AN: 31102

American (AMR) AF: 0.692 AC: 24581 AN: 35520

Ashkenazi Jewish (ASJ) AF: 0.708 AC: 16081 AN: 22708

East Asian (EAS) AF: 0.759 AC: 28871 AN: 38048

South Asian (SAS) AF: 0.626 AC: 48683 AN: 77714

European-Finnish (FIN) AF: 0.775 AC: 37872 AN: 48858

Middle Eastern (MID) AF: 0.725 AC: 3497 AN: 4826

European-Non Finnish (NFE) AF: 0.770 AC: 807176 AN: 1048040

Other (OTH) AF: 0.754 AC: 42389 AN: 56216

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

African (AFR) AF: 0.911 AC: 37797 AN: 41502

American (AMR) AF: 0.710 AC: 10857 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.697 AC: 2419 AN: 3470

East Asian (EAS) AF: 0.774 AC: 3950 AN: 5102

South Asian (SAS) AF: 0.626 AC: 3009 AN: 4806

European-Finnish (FIN) AF: 0.780 AC: 8242 AN: 10568

Middle Eastern (MID) AF: 0.677 AC: 199 AN: 294

European-Non Finnish (NFE) AF: 0.765 AC: 51970 AN: 67938

Other (OTH) AF: 0.770 AC: 1626 AN: 2112

Alfa AF: 0.773 Hom.: 66725

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
PhyloP100		-0.33
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2234753; hg19: chr9-137293761;