rs10776909

chr9-134396900-T-Cchr9-134396900-T-G

Variant summary

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

The NM_002957.6(RXRA):c.29-4732T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.822 in 152,228 control chromosomes in the GnomAD database, including 51,829 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 0.82 (51829 hom., cov: 33)
• Consequence: RXRA NM_002957.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.27

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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.918 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RXRA	NM_002957.6	c.29-4732T>C		intron_variant		ENST00000481739.2
RXRA	NM_001291920.2	c.-53-4732T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RXRA	ENST00000481739.2	c.29-4732T>C		intron_variant		1	NM_002957.6	P3

Frequencies

GnomAD3 genomes AF: 0.822 AC: 125082 AN: 152110 Hom.: 51786 Cov.: 33

Gnomad AFR AF: 0.926

Gnomad AMI AF: 0.864

Gnomad AMR AF: 0.759

Gnomad ASJ AF: 0.731

Gnomad EAS AF: 0.796

Gnomad SAS AF: 0.660

Gnomad FIN AF: 0.808

Gnomad MID AF: 0.690

Gnomad NFE AF: 0.794

Gnomad OTH AF: 0.802

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

GnomAD4 genome AF: 0.822 AC: 125184 AN: 152228 Hom.: 51829 Cov.: 33 AF XY: 0.819 AC XY: 60957 AN XY: 74440

Gnomad4 AFR AF: 0.926

Gnomad4 AMR AF: 0.759

Gnomad4 ASJ AF: 0.731

Gnomad4 EAS AF: 0.796

Gnomad4 SAS AF: 0.659

Gnomad4 FIN AF: 0.808

Gnomad4 NFE AF: 0.794

Gnomad4 OTH AF: 0.799

Alfa AF: 0.786 Hom.: 32166

Bravo AF: 0.824

Asia WGS AF: 0.737 AC: 2565 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	1.3
Dann	Benign	0.48

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: rs10776909; hg19: chr9-137288746; COSMIC: COSV62683862;