rs4917353

Positions:

• chr9-134345449-T-A
• chr9-134345449-T-C
• chr9-134345449-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.28+18790T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.418 in 152,046 control chromosomes in the GnomAD database, including 15,906 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 0.42 (15906 hom., cov: 32)
• Consequence: RXRA NM_002957.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.201

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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.701 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RXRA	NM_002957.6	c.28+18790T>A		intron_variant		ENST00000481739.2	NP_002948.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RXRA	ENST00000481739.2	c.28+18790T>A		intron_variant		1	NM_002957.6	ENSP00000419692	P3
RXRA	ENST00000484822.1	n.452+25965T>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.417 AC: 63384 AN: 151928 Hom.: 15863 Cov.: 32

Gnomad AFR AF: 0.707

Gnomad AMI AF: 0.226

Gnomad AMR AF: 0.387

Gnomad ASJ AF: 0.292

Gnomad EAS AF: 0.215

Gnomad SAS AF: 0.312

Gnomad FIN AF: 0.279

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.302

Gnomad OTH AF: 0.402

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

GnomAD4 genome AF: 0.418 AC: 63489 AN: 152046 Hom.: 15906 Cov.: 32 AF XY: 0.411 AC XY: 30561 AN XY: 74322

Gnomad4 AFR AF: 0.708

Gnomad4 AMR AF: 0.387

Gnomad4 ASJ AF: 0.292

Gnomad4 EAS AF: 0.215

Gnomad4 SAS AF: 0.312

Gnomad4 FIN AF: 0.279

Gnomad4 NFE AF: 0.302

Gnomad4 OTH AF: 0.404

Alfa AF: 0.353 Hom.: 1343

Bravo AF: 0.440

Asia WGS AF: 0.301 AC: 1044 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	2.1
DANN	Benign	0.57
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		2.2

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: rs4917353; hg19: chr9-137237295;