rs11103473

Positions:

• chr9-134395783-T-A
• chr9-134395783-T-C

Variant summary

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

The NM_002957.6(RXRA):​c.29-5849T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.526 in 152,190 control chromosomes in the GnomAD database, including 23,143 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 0.53 (23143 hom., cov: 35)
• Consequence: RXRA NM_002957.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0330

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]

RXRA (HGNC:):

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 (EAS) allele frequency at 95% confidence interval = 0.714 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RXRA	NM_002957.6	c.29-5849T>A		intron_variant		ENST00000481739.2	NP_002948.1
RXRA	NM_001291920.2	c.-53-5849T>A		intron_variant			NP_001278849.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RXRA	ENST00000481739.2	c.29-5849T>A		intron_variant		1	NM_002957.6	ENSP00000419692.1

Frequencies

GnomAD3 genomes AF: 0.527 AC: 80070 AN: 152070 Hom.: 23148 Cov.: 35

Gnomad AFR AF: 0.272

Gnomad AMI AF: 0.650

Gnomad AMR AF: 0.562

Gnomad ASJ AF: 0.613

Gnomad EAS AF: 0.734

Gnomad SAS AF: 0.465

Gnomad FIN AF: 0.593

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.644

Gnomad OTH AF: 0.571

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

GnomAD4 genome AF: 0.526 AC: 80084 AN: 152190 Hom.: 23143 Cov.: 35 AF XY: 0.525 AC XY: 39092 AN XY: 74402

Gnomad4 AFR AF: 0.272

Gnomad4 AMR AF: 0.562

Gnomad4 ASJ AF: 0.613

Gnomad4 EAS AF: 0.734

Gnomad4 SAS AF: 0.465

Gnomad4 FIN AF: 0.593

Gnomad4 NFE AF: 0.644

Gnomad4 OTH AF: 0.567

Alfa AF: 0.465 Hom.: 1456

Bravo AF: 0.518

Asia WGS AF: 0.591 AC: 2056 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	6.5
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: rs11103473; hg19: chr9-137287629; COSMIC: COSV62683853;