9-134440465-T-G

Position:

• chr9-134440465-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.*3851T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.861 in 152,684 control chromosomes in the GnomAD database, including 56,832 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 0.86 (56712 hom., cov: 35)
  • Exomes 𝑓: 0.81 (120 hom.)
• Consequence: RXRA NM_002957.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.605

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.953 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RXRA	NM_002957.6	c.*3851T>G		3_prime_UTR_variant	10/10	ENST00000481739.2	NP_002948.1
RXRA	NM_001291920.2	c.*3851T>G		3_prime_UTR_variant	10/10		NP_001278849.1
RXRA	NM_001291921.2	c.*3851T>G		3_prime_UTR_variant	9/9		NP_001278850.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RXRA	ENST00000481739.2	c.*3851T>G		3_prime_UTR_variant	10/10	1	NM_002957.6	ENSP00000419692.1
RXRA	ENST00000356384.4	n.5650T>G		non_coding_transcript_exon_variant	12/12	5

Frequencies

GnomAD3 genomes AF: 0.861 AC: 130994 AN: 152198 Hom.: 56670 Cov.: 35

Gnomad AFR AF: 0.961

Gnomad AMI AF: 0.900

Gnomad AMR AF: 0.817

Gnomad ASJ AF: 0.816

Gnomad EAS AF: 0.825

Gnomad SAS AF: 0.690

Gnomad FIN AF: 0.828

Gnomad MID AF: 0.826

Gnomad NFE AF: 0.832

Gnomad OTH AF: 0.845

GnomAD4 exome AF: 0.813 AC: 299 AN: 368 Hom.: 120 Cov.: 0 AF XY: 0.812 AC XY: 177 AN XY: 218

Gnomad4 AFR exome AF: 1.00

Gnomad4 ASJ exome AF: 1.00

Gnomad4 EAS exome AF: 0.750

Gnomad4 FIN exome AF: 0.807

Gnomad4 NFE exome AF: 0.804

Gnomad4 OTH exome AF: 1.00

GnomAD4 genome AF: 0.861 AC: 131093 AN: 152316 Hom.: 56712 Cov.: 35 AF XY: 0.857 AC XY: 63802 AN XY: 74472

Gnomad4 AFR AF: 0.961

Gnomad4 AMR AF: 0.817

Gnomad4 ASJ AF: 0.816

Gnomad4 EAS AF: 0.825

Gnomad4 SAS AF: 0.689

Gnomad4 FIN AF: 0.828

Gnomad4 NFE AF: 0.832

Gnomad4 OTH AF: 0.841

Alfa AF: 0.828 Hom.: 34549

Bravo AF: 0.867

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.041
DANN	Benign	0.54

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1045570; hg19: chr9-137332311; COSMIC: COSV62683924;