rs1805352

chr9-134408103-C-A

Variant summary

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

The NM_002957.6(RXRA):c.280-46C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.66 in 1,460,986 control chromosomes in the GnomAD database, including 324,488 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 0.58 (27290 hom., cov: 30)
  • Exomes 𝑓: 0.67 (297198 hom.)
• Consequence: RXRA NM_002957.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.60

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=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.739 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RXRA	NM_002957.6	c.280-46C>A		intron_variant		ENST00000481739.2
RXRA	NM_001291920.2	c.199-46C>A		intron_variant
RXRA	NM_001291921.2	c.-12-46C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RXRA	ENST00000481739.2	c.280-46C>A		intron_variant		1	NM_002957.6	P3
RXRA	ENST00000672570.1	c.199-46C>A		intron_variant				A1
RXRA	ENST00000356384.4	n.690-46C>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.579 AC: 87649 AN: 151414 Hom.: 27290 Cov.: 30

Gnomad AFR AF: 0.330

Gnomad AMI AF: 0.748

Gnomad AMR AF: 0.629

Gnomad ASJ AF: 0.672

Gnomad EAS AF: 0.759

Gnomad SAS AF: 0.476

Gnomad FIN AF: 0.691

Gnomad MID AF: 0.598

Gnomad NFE AF: 0.686

Gnomad OTH AF: 0.621

GnomAD3 exomes AF: 0.630 AC: 94536 AN: 149996 Hom.: 30824 AF XY: 0.634 AC XY: 51333 AN XY: 80958

Gnomad AFR exome AF: 0.317

Gnomad AMR exome AF: 0.617

Gnomad ASJ exome AF: 0.681

Gnomad EAS exome AF: 0.751

Gnomad SAS exome AF: 0.461

Gnomad FIN exome AF: 0.691

Gnomad NFE exome AF: 0.680

Gnomad OTH exome AF: 0.646

GnomAD4 exome AF: 0.669 AC: 876005 AN: 1309454 Hom.: 297198 Cov.: 22 AF XY: 0.664 AC XY: 426881 AN XY: 642824

Gnomad4 AFR exome AF: 0.308

Gnomad4 AMR exome AF: 0.625

Gnomad4 ASJ exome AF: 0.690

Gnomad4 EAS exome AF: 0.757

Gnomad4 SAS exome AF: 0.475

Gnomad4 FIN exome AF: 0.690

Gnomad4 NFE exome AF: 0.689

Gnomad4 OTH exome AF: 0.654

GnomAD4 genome AF: 0.579 AC: 87672 AN: 151532 Hom.: 27290 Cov.: 30 AF XY: 0.580 AC XY: 42926 AN XY: 74024

Gnomad4 AFR AF: 0.330

Gnomad4 AMR AF: 0.630

Gnomad4 ASJ AF: 0.672

Gnomad4 EAS AF: 0.759

Gnomad4 SAS AF: 0.476

Gnomad4 FIN AF: 0.691

Gnomad4 NFE AF: 0.686

Gnomad4 OTH AF: 0.615

Alfa AF: 0.651 Hom.: 27474

Bravo AF: 0.568

Asia WGS AF: 0.601 AC: 2092 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	0.074
Dann	Benign	0.40

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs1805352; hg19: chr9-137299949; COSMIC: COSV62685276; COSMIC: COSV62685276;