rs4842194

Positions:

• chr9-134438714-C-T

Variant summary

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

The NM_002957.6(RXRA):​c.*2100C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.544 in 153,130 control chromosomes in the GnomAD database, including 24,567 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 0.54 (24391 hom., cov: 35)
  • Exomes 𝑓: 0.61 (176 hom.)
• Consequence: RXRA NM_002957.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.243

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=-0.72).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.65 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RXRA	NM_002957.6	c.*2100C>T		3_prime_UTR_variant	10/10	ENST00000481739.2	NP_002948.1
RXRA	NM_001291920.2	c.*2100C>T		3_prime_UTR_variant	10/10		NP_001278849.1
RXRA	NM_001291921.2	c.*2100C>T		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.*2100C>T		3_prime_UTR_variant	10/10	1	NM_002957.6	ENSP00000419692	P3
RXRA	ENST00000356384.4	n.3899C>T		non_coding_transcript_exon_variant	12/12	5

Frequencies

GnomAD3 genomes AF: 0.544 AC: 82762 AN: 152106 Hom.: 24391 Cov.: 35

Gnomad AFR AF: 0.302

Gnomad AMI AF: 0.655

Gnomad AMR AF: 0.581

Gnomad ASJ AF: 0.644

Gnomad EAS AF: 0.656

Gnomad SAS AF: 0.495

Gnomad FIN AF: 0.641

Gnomad MID AF: 0.547

Gnomad NFE AF: 0.656

Gnomad OTH AF: 0.572

GnomAD4 exome AF: 0.615 AC: 557 AN: 906 Hom.: 176 Cov.: 0 AF XY: 0.622 AC XY: 311 AN XY: 500

Gnomad4 AFR exome AF: 0.200

Gnomad4 AMR exome AF: 0.500

Gnomad4 ASJ exome AF: 0.667

Gnomad4 EAS exome AF: 0.662

Gnomad4 FIN exome AF: 0.641

Gnomad4 NFE exome AF: 0.609

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.544 AC: 82771 AN: 152224 Hom.: 24391 Cov.: 35 AF XY: 0.545 AC XY: 40581 AN XY: 74412

Gnomad4 AFR AF: 0.302

Gnomad4 AMR AF: 0.581

Gnomad4 ASJ AF: 0.644

Gnomad4 EAS AF: 0.656

Gnomad4 SAS AF: 0.494

Gnomad4 FIN AF: 0.641

Gnomad4 NFE AF: 0.656

Gnomad4 OTH AF: 0.566

Alfa AF: 0.509 Hom.: 2434

Bravo AF: 0.532

Asia WGS AF: 0.567 AC: 1975 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	8.0
DANN	Benign	0.94

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4842194; hg19: chr9-137330560;