9-134398879-G-T

Position:

• chr9-134398879-G-T

Variant summary

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

The NM_002957.6(RXRA):​c.29-2753G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.129 in 152,266 control chromosomes in the GnomAD database, including 1,356 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 0.13 (1356 hom., cov: 34)
• Consequence: RXRA NM_002957.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.18

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=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.16 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RXRA	NM_002957.6	c.29-2753G>T		intron_variant		ENST00000481739.2
RXRA	NM_001291920.2	c.-53-2753G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RXRA	ENST00000481739.2	c.29-2753G>T		intron_variant		1	NM_002957.6	P3

Frequencies

GnomAD3 genomes AF: 0.129 AC: 19639 AN: 152148 Hom.: 1356 Cov.: 34

Gnomad AFR AF: 0.164

Gnomad AMI AF: 0.122

Gnomad AMR AF: 0.0842

Gnomad ASJ AF: 0.0998

Gnomad EAS AF: 0.0569

Gnomad SAS AF: 0.168

Gnomad FIN AF: 0.165

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.118

Gnomad OTH AF: 0.103

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

GnomAD4 genome AF: 0.129 AC: 19646 AN: 152266 Hom.: 1356 Cov.: 34 AF XY: 0.131 AC XY: 9753 AN XY: 74472

Gnomad4 AFR AF: 0.163

Gnomad4 AMR AF: 0.0840

Gnomad4 ASJ AF: 0.0998

Gnomad4 EAS AF: 0.0574

Gnomad4 SAS AF: 0.168

Gnomad4 FIN AF: 0.165

Gnomad4 NFE AF: 0.118

Gnomad4 OTH AF: 0.103

Alfa AF: 0.102 Hom.: 810

Bravo AF: 0.122

Asia WGS AF: 0.0970 AC: 335 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.34
DANN	Benign	0.68

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: rs12004589; hg19: chr9-137290725;