chr9-134319017-T-C

Position:

• chr9-134319017-T-C

Variant summary

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

The ENST00000484822.1(RXRA):​n.406-421T>C 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 0.273 in 152,200 control chromosomes in the GnomAD database, including 7,828 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as drug response (no stars).

• Frequency: Genomes: 𝑓 0.27 (7828 hom., cov: 33)
• Consequence: RXRA ENST00000484822.1 intron, non_coding_transcript
• Clinical Significance: drug response no assertion criteria provided O:1
• Conservation: PhyloP100: -3.36

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.521 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.406-421T>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.273 AC: 41444 AN: 152082 Hom.: 7817 Cov.: 33

Gnomad AFR AF: 0.527

Gnomad AMI AF: 0.105

Gnomad AMR AF: 0.301

Gnomad ASJ AF: 0.209

Gnomad EAS AF: 0.0673

Gnomad SAS AF: 0.0776

Gnomad FIN AF: 0.112

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.171

Gnomad OTH AF: 0.272

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

GnomAD4 genome AF: 0.273 AC: 41501 AN: 152200 Hom.: 7828 Cov.: 33 AF XY: 0.266 AC XY: 19789 AN XY: 74410

Gnomad4 AFR AF: 0.527

Gnomad4 AMR AF: 0.301

Gnomad4 ASJ AF: 0.209

Gnomad4 EAS AF: 0.0669

Gnomad4 SAS AF: 0.0778

Gnomad4 FIN AF: 0.112

Gnomad4 NFE AF: 0.171

Gnomad4 OTH AF: 0.275

Alfa AF: 0.190 Hom.: 3342

Bravo AF: 0.303

Asia WGS AF: 0.105 AC: 365 AN: 3478

ClinVar

Significance: drug response

Submissions summary: Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Levothyroxine response Other:1

drug response, no assertion criteria provided

research

Pharmacogenomics/Precision medicine lab, University of Petra

-

- The CT genotype was predictive of T3 dosage requirements

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.016
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: rs11185644; hg19: chr9-137210863;