NM_002957.6:c.29-26039T>C

Variant names:

• chr9-134375593-T-C
• rs10881583
• NM_002957.6:c.29-26039T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002957.6(RXRA):​c.29-26039T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.366 in 151,914 control chromosomes in the GnomAD database, including 12,912 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 0.37 (12912 hom., cov: 32)
• Consequence: RXRA NM_002957.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.439
• 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.655 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002957.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RXRA	NM_002957.6	MANE Select	c.29-26039T>C		intron	N/A	NP_002948.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RXRA	ENST00000481739.2	TSL:1 MANE Select	c.29-26039T>C		intron	N/A	ENSP00000419692.1
	RXRA	ENST00000356384.4	TSL:5	n.293+1463T>C		intron	N/A
	RXRA	ENST00000484822.1	TSL:2	n.453-26039T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.366 AC: 55565 AN: 151796 Hom.: 12868 Cov.: 32

Gnomad AFR AF: 0.662

Gnomad AMI AF: 0.178

Gnomad AMR AF: 0.366

Gnomad ASJ AF: 0.272

Gnomad EAS AF: 0.188

Gnomad SAS AF: 0.226

Gnomad FIN AF: 0.243

Gnomad MID AF: 0.347

Gnomad NFE AF: 0.237

Gnomad OTH AF: 0.345

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

GnomAD4 genome AF: 0.366 AC: 55670 AN: 151914 Hom.: 12912 Cov.: 32 AF XY: 0.362 AC XY: 26849 AN XY: 74246

African (AFR) AF: 0.662 AC: 27416 AN: 41422

American (AMR) AF: 0.366 AC: 5578 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.272 AC: 942 AN: 3468

East Asian (EAS) AF: 0.188 AC: 968 AN: 5148

South Asian (SAS) AF: 0.227 AC: 1089 AN: 4806

European-Finnish (FIN) AF: 0.243 AC: 2566 AN: 10554

Middle Eastern (MID) AF: 0.336 AC: 98 AN: 292

European-Non Finnish (NFE) AF: 0.237 AC: 16116 AN: 67950

Other (OTH) AF: 0.349 AC: 735 AN: 2104

Alfa AF: 0.352 Hom.: 3178

Bravo AF: 0.393

Asia WGS AF: 0.252 AC: 876 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.2
DANN	Benign	0.35
PhyloP100		-0.44
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
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: rs10881583; hg19: chr9-137267439;