rs4917348

Positions:

• chr9-134322299-A-G

Variant summary

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

The ENST00000484822.1(RXRA):​n.452+2815A>G variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.281 in 152,090 control chromosomes in the GnomAD database, including 8,494 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 0.28 (8494 hom., cov: 33)
• Consequence: RXRA ENST00000484822.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.171

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.55 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RXRA	ENST00000484822.1	n.452+2815A>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.281 AC: 42662 AN: 151976 Hom.: 8476 Cov.: 33

Gnomad AFR AF: 0.556

Gnomad AMI AF: 0.105

Gnomad AMR AF: 0.306

Gnomad ASJ AF: 0.208

Gnomad EAS AF: 0.0664

Gnomad SAS AF: 0.0774

Gnomad FIN AF: 0.112

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.171

Gnomad OTH AF: 0.278

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

GnomAD4 genome AF: 0.281 AC: 42738 AN: 152090 Hom.: 8494 Cov.: 33 AF XY: 0.274 AC XY: 20371 AN XY: 74330

Gnomad4 AFR AF: 0.556

Gnomad4 AMR AF: 0.306

Gnomad4 ASJ AF: 0.208

Gnomad4 EAS AF: 0.0660

Gnomad4 SAS AF: 0.0777

Gnomad4 FIN AF: 0.112

Gnomad4 NFE AF: 0.171

Gnomad4 OTH AF: 0.280

Alfa AF: 0.210 Hom.: 948

Bravo AF: 0.313

Asia WGS AF: 0.109 AC: 380 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.8
DANN	Benign	0.47

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4917348; hg19: chr9-137214145;