rs1805352

Variant names:

• chr9-134408103-C-A
• rs1805352
• NM_002957.6:c.280-46C>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 30 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
RXRA	NM_002957.6	c.280-46C>A		intron_variant	Intron 2 of 9	ENST00000481739.2	NP_002948.1
RXRA	NM_001291920.2	c.199-46C>A		intron_variant	Intron 2 of 9		NP_001278849.1
RXRA	NM_001291921.2	c.-12-46C>A		intron_variant	Intron 1 of 8		NP_001278850.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RXRA	ENST00000481739.2	c.280-46C>A		intron_variant	Intron 2 of 9	1	NM_002957.6	ENSP00000419692.1
RXRA	ENST00000672570.1	c.199-46C>A		intron_variant	Intron 2 of 9			ENSP00000500402.1
RXRA	ENST00000356384.4	n.690-46C>A		intron_variant	Intron 4 of 11	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

GnomAD2 exomes AF: 0.630 AC: 94536 AN: 149996 AF XY: 0.634

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 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

African (AFR) AF: 0.308 AC: 8691 AN: 28258

American (AMR) AF: 0.625 AC: 15074 AN: 24114

Ashkenazi Jewish (ASJ) AF: 0.690 AC: 13121 AN: 19026

East Asian (EAS) AF: 0.757 AC: 25961 AN: 34308

South Asian (SAS) AF: 0.475 AC: 31107 AN: 65506

European-Finnish (FIN) AF: 0.690 AC: 33160 AN: 48090

Middle Eastern (MID) AF: 0.618 AC: 3198 AN: 5176

European-Non Finnish (NFE) AF: 0.689 AC: 710545 AN: 1031232

Other (OTH) AF: 0.654 AC: 35148 AN: 53744

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

African (AFR) AF: 0.330 AC: 13585 AN: 41164

American (AMR) AF: 0.630 AC: 9620 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.672 AC: 2329 AN: 3468

East Asian (EAS) AF: 0.759 AC: 3864 AN: 5094

South Asian (SAS) AF: 0.476 AC: 2287 AN: 4806

European-Finnish (FIN) AF: 0.691 AC: 7295 AN: 10558

Middle Eastern (MID) AF: 0.609 AC: 179 AN: 294

European-Non Finnish (NFE) AF: 0.686 AC: 46542 AN: 67862

Other (OTH) AF: 0.615 AC: 1293 AN: 2102

Alfa AF: 0.648 Hom.: 31763

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
PhyloP100		-1.6
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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