9-134426332-C-T

Variant names:

• chr9-134426332-C-T
• rs3118571
• NM_002957.6:c.911-2776C>T

Variant summary

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

The NM_002957.6(RXRA):​c.911-2776C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.622 in 985,246 control chromosomes in the GnomAD database, including 196,301 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 0.52 (23179 hom., cov: 33)
  • Exomes 𝑓: 0.64 (173122 hom.)
• Consequence: RXRA NM_002957.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.677

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.673 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RXRA	NM_002957.6	c.911-2776C>T		intron_variant	Intron 6 of 9	ENST00000481739.2	NP_002948.1
RXRA	NM_001291920.2	c.830-2776C>T		intron_variant	Intron 6 of 9		NP_001278849.1
RXRA	NM_001291921.2	c.620-2776C>T		intron_variant	Intron 5 of 8		NP_001278850.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RXRA	ENST00000481739.2	c.911-2776C>T		intron_variant	Intron 6 of 9	1	NM_002957.6	ENSP00000419692.1
RXRA	ENST00000672570.1	c.830-2776C>T		intron_variant	Intron 6 of 9			ENSP00000500402.1
RXRA	ENST00000356384.4	n.1321-2776C>T		intron_variant	Intron 8 of 11	5

Frequencies

GnomAD3 genomes AF: 0.516 AC: 78525 AN: 152040 Hom.: 23182 Cov.: 33

Gnomad AFR AF: 0.210

Gnomad AMI AF: 0.705

Gnomad AMR AF: 0.568

Gnomad ASJ AF: 0.653

Gnomad EAS AF: 0.693

Gnomad SAS AF: 0.497

Gnomad FIN AF: 0.631

Gnomad MID AF: 0.582

Gnomad NFE AF: 0.651

Gnomad OTH AF: 0.554

GnomAD4 exome AF: 0.641 AC: 533971 AN: 833086 Hom.: 173122 Cov.: 38 AF XY: 0.640 AC XY: 246333 AN XY: 384708

Gnomad4 AFR exome AF: 0.175

Gnomad4 AMR exome AF: 0.578

Gnomad4 ASJ exome AF: 0.667

Gnomad4 EAS exome AF: 0.685

Gnomad4 SAS exome AF: 0.492

Gnomad4 FIN exome AF: 0.627

Gnomad4 NFE exome AF: 0.654

Gnomad4 OTH exome AF: 0.621

GnomAD4 genome AF: 0.516 AC: 78523 AN: 152160 Hom.: 23179 Cov.: 33 AF XY: 0.519 AC XY: 38612 AN XY: 74388

Gnomad4 AFR AF: 0.210

Gnomad4 AMR AF: 0.568

Gnomad4 ASJ AF: 0.653

Gnomad4 EAS AF: 0.692

Gnomad4 SAS AF: 0.496

Gnomad4 FIN AF: 0.631

Gnomad4 NFE AF: 0.651

Gnomad4 OTH AF: 0.548

Alfa AF: 0.620 Hom.: 38096

Bravo AF: 0.501

Asia WGS AF: 0.559 AC: 1945 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.71
DANN	Benign	0.47

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

Publications

LitVar

Other links and lift over

dbSNP: rs3118571; hg19: chr9-137318178;