rs749759

chr9-134432806-A-Gchr9-134432806-A-T

Variant summary

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

The NM_002957.6(RXRA):c.1135+810A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.811 in 152,104 control chromosomes in the GnomAD database, including 50,579 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 0.81 (50579 hom., cov: 32)
• Consequence: RXRA NM_002957.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0370

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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.939 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RXRA	NM_002957.6	c.1135+810A>G		intron_variant		ENST00000481739.2
RXRA	NM_001291920.2	c.1054+810A>G		intron_variant
RXRA	NM_001291921.2	c.844+810A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RXRA	ENST00000481739.2	c.1135+810A>G		intron_variant		1	NM_002957.6	P3
RXRA	ENST00000672570.1	c.1054+810A>G		intron_variant				A1
RXRA	ENST00000356384.4	n.1545+810A>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.811 AC: 123241 AN: 151986 Hom.: 50534 Cov.: 32

Gnomad AFR AF: 0.947

Gnomad AMI AF: 0.898

Gnomad AMR AF: 0.775

Gnomad ASJ AF: 0.712

Gnomad EAS AF: 0.815

Gnomad SAS AF: 0.663

Gnomad FIN AF: 0.763

Gnomad MID AF: 0.687

Gnomad NFE AF: 0.759

Gnomad OTH AF: 0.788

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

GnomAD4 genome AF: 0.811 AC: 123341 AN: 152104 Hom.: 50579 Cov.: 32 AF XY: 0.809 AC XY: 60108 AN XY: 74342

Gnomad4 AFR AF: 0.947

Gnomad4 AMR AF: 0.775

Gnomad4 ASJ AF: 0.712

Gnomad4 EAS AF: 0.815

Gnomad4 SAS AF: 0.661

Gnomad4 FIN AF: 0.763

Gnomad4 NFE AF: 0.759

Gnomad4 OTH AF: 0.785

Alfa AF: 0.793 Hom.: 5952

Bravo AF: 0.818

Asia WGS AF: 0.755 AC: 2626 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.97
Dann	Benign	0.27

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: rs749759; hg19: chr9-137324652; COSMIC: COSV62683915;