rs10881582

Variant names:

• chr9-134364232-G-A
• rs10881582
• NM_002957.6:c.29-37400G>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.29-37400G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.364 in 152,200 control chromosomes in the GnomAD database, including 12,772 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 0.36 (12772 hom., cov: 34)
• Consequence: RXRA NM_002957.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.985
• Publications: 26 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.652 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RXRA	NM_002957.6	c.29-37400G>A		intron_variant	Intron 1 of 9	ENST00000481739.2	NP_002948.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RXRA	ENST00000481739.2	c.29-37400G>A		intron_variant	Intron 1 of 9	1	NM_002957.6	ENSP00000419692.1
RXRA	ENST00000484822.1	n.453-37400G>A		intron_variant	Intron 2 of 2	2

Frequencies

GnomAD3 genomes AF: 0.363 AC: 55212 AN: 152082 Hom.: 12721 Cov.: 34

Gnomad AFR AF: 0.658

Gnomad AMI AF: 0.183

Gnomad AMR AF: 0.365

Gnomad ASJ AF: 0.257

Gnomad EAS AF: 0.176

Gnomad SAS AF: 0.226

Gnomad FIN AF: 0.242

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.235

Gnomad OTH AF: 0.341

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.364 AC: 55325 AN: 152200 Hom.: 12772 Cov.: 34 AF XY: 0.358 AC XY: 26687 AN XY: 74446

African (AFR) AF: 0.658 AC: 27307 AN: 41492

American (AMR) AF: 0.365 AC: 5586 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.257 AC: 892 AN: 3472

East Asian (EAS) AF: 0.176 AC: 910 AN: 5172

South Asian (SAS) AF: 0.226 AC: 1091 AN: 4826

European-Finnish (FIN) AF: 0.242 AC: 2575 AN: 10620

Middle Eastern (MID) AF: 0.330 AC: 97 AN: 294

European-Non Finnish (NFE) AF: 0.235 AC: 15970 AN: 68004

Other (OTH) AF: 0.345 AC: 730 AN: 2114

Alfa AF: 0.281 Hom.: 12324

Bravo AF: 0.390

Asia WGS AF: 0.249 AC: 863 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.17
DANN	Benign	0.46
PhyloP100		-0.98
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs10881582; hg19: chr9-137256078;