rs1536475

Variant names:

• chr9-134429310-A-G
• rs1536475
• NM_002957.6:c.1043+70A>G

Your query was ambiguous. Multiple possible variants found:

• chr9-134429310-A-G
• chr9-134429310-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002957.6(RXRA):​c.1043+70A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.815 in 1,529,316 control chromosomes in the GnomAD database, including 510,233 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 0.85 (55629 hom., cov: 34)
  • Exomes 𝑓: 0.81 (454604 hom.)
• Consequence: RXRA NM_002957.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.89
• Publications: 24 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]

RXRA Gene-Disease associations (from GenCC):

• congenital heart disease

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.952 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002957.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RXRA	NM_002957.6	MANE Select	c.1043+70A>G		intron	N/A	NP_002948.1	P19793-1
	RXRA	NM_001291920.2		c.962+70A>G		intron	N/A	NP_001278849.1	A0A5F9ZHH6
	RXRA	NM_001291921.2		c.752+70A>G		intron	N/A	NP_001278850.1	P19793-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RXRA	ENST00000481739.2	TSL:1 MANE Select	c.1043+70A>G		intron	N/A	ENSP00000419692.1	P19793-1
	RXRA	ENST00000672570.1		c.962+70A>G		intron	N/A	ENSP00000500402.1	A0A5F9ZHH6
	RXRA	ENST00000356384.4	TSL:5	n.1453+70A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.851 AC: 129517 AN: 152140 Hom.: 55572 Cov.: 34

Gnomad AFR AF: 0.960

Gnomad AMI AF: 0.910

Gnomad AMR AF: 0.804

Gnomad ASJ AF: 0.766

Gnomad EAS AF: 0.758

Gnomad SAS AF: 0.684

Gnomad FIN AF: 0.853

Gnomad MID AF: 0.693

Gnomad NFE AF: 0.820

Gnomad OTH AF: 0.819

GnomAD4 exome AF: 0.811 AC: 1116858 AN: 1377058 Hom.: 454604 AF XY: 0.806 AC XY: 551492 AN XY: 684540

African (AFR) AF: 0.966 AC: 30567 AN: 31652

American (AMR) AF: 0.755 AC: 30569 AN: 40480

Ashkenazi Jewish (ASJ) AF: 0.785 AC: 19034 AN: 24258

East Asian (EAS) AF: 0.745 AC: 28957 AN: 38870

South Asian (SAS) AF: 0.670 AC: 55589 AN: 82982

European-Finnish (FIN) AF: 0.839 AC: 34960 AN: 41652

Middle Eastern (MID) AF: 0.729 AC: 3930 AN: 5388

European-Non Finnish (NFE) AF: 0.822 AC: 867017 AN: 1054474

Other (OTH) AF: 0.807 AC: 46235 AN: 57302

GnomAD4 genome AF: 0.851 AC: 129629 AN: 152258 Hom.: 55629 Cov.: 34 AF XY: 0.849 AC XY: 63246 AN XY: 74452

African (AFR) AF: 0.960 AC: 39904 AN: 41574

American (AMR) AF: 0.804 AC: 12305 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.766 AC: 2658 AN: 3470

East Asian (EAS) AF: 0.758 AC: 3908 AN: 5158

South Asian (SAS) AF: 0.683 AC: 3297 AN: 4826

European-Finnish (FIN) AF: 0.853 AC: 9049 AN: 10614

Middle Eastern (MID) AF: 0.704 AC: 207 AN: 294

European-Non Finnish (NFE) AF: 0.820 AC: 55752 AN: 67994

Other (OTH) AF: 0.815 AC: 1721 AN: 2112

Alfa AF: 0.820 Hom.: 124884

Bravo AF: 0.853

Asia WGS AF: 0.732 AC: 2549 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.087
DANN	Benign	0.33
PhyloP100		-4.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1536475;

hg19: chr9-137321156;

COSMIC: COSV62683908;