chr9-134323982-G-A

Variant names:

• chr9-134323982-G-A
• rs11185647
• ENST00000484822.1:n.452+4498G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000484822.1(RXRA):​n.452+4498G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.409 in 152,092 control chromosomes in the GnomAD database, including 15,496 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 0.41 (15496 hom., cov: 32)
• Consequence: RXRA ENST00000484822.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.283
• Publications: 11 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.699 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RXRA	ENST00000484822.1	n.452+4498G>A		intron_variant	Intron 2 of 2	2

Frequencies

GnomAD3 genomes AF: 0.409 AC: 62148 AN: 151974 Hom.: 15448 Cov.: 32

Gnomad AFR AF: 0.705

Gnomad AMI AF: 0.217

Gnomad AMR AF: 0.383

Gnomad ASJ AF: 0.282

Gnomad EAS AF: 0.212

Gnomad SAS AF: 0.298

Gnomad FIN AF: 0.266

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.289

Gnomad OTH AF: 0.393

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

GnomAD4 genome AF: 0.409 AC: 62264 AN: 152092 Hom.: 15496 Cov.: 32 AF XY: 0.404 AC XY: 30009 AN XY: 74344

African (AFR) AF: 0.706 AC: 29274 AN: 41470

American (AMR) AF: 0.383 AC: 5855 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.282 AC: 978 AN: 3470

East Asian (EAS) AF: 0.212 AC: 1098 AN: 5176

South Asian (SAS) AF: 0.298 AC: 1437 AN: 4822

European-Finnish (FIN) AF: 0.266 AC: 2813 AN: 10570

Middle Eastern (MID) AF: 0.327 AC: 96 AN: 294

European-Non Finnish (NFE) AF: 0.289 AC: 19671 AN: 67976

Other (OTH) AF: 0.399 AC: 844 AN: 2114

Alfa AF: 0.337 Hom.: 24852

Bravo AF: 0.433

Asia WGS AF: 0.286 AC: 992 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.7
DANN	Benign	0.74
PhyloP100		0.28

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs11185647; hg19: chr9-137215828;