9-134406969-C-G

Variant names:

• chr9-134406969-C-G
• rs3132299
• NM_002957.6:c.280-1180C>G

Variant summary

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

The NM_001291921.2(RXRA):​c.-536C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.848 in 152,178 control chromosomes in the GnomAD database, including 55,143 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 (55143 hom., cov: 32)
• Consequence: RXRA NM_001291921.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.234
• Publications: 10 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.946 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001291921.2. 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.280-1180C>G		intron	N/A	NP_002948.1	P19793-1
	RXRA	NM_001291921.2		c.-536C>G		5_prime_UTR	Exon 1 of 9	NP_001278850.1	P19793-2
	RXRA	NM_001291920.2		c.199-1180C>G		intron	N/A	NP_001278849.1	A0A5F9ZHH6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RXRA	ENST00000481739.2	TSL:1 MANE Select	c.280-1180C>G		intron	N/A	ENSP00000419692.1	P19793-1
	RXRA	ENST00000672570.1		c.199-1180C>G		intron	N/A	ENSP00000500402.1	A0A5F9ZHH6
	RXRA	ENST00000356384.4	TSL:5	n.690-1180C>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.848 AC: 128973 AN: 152060 Hom.: 55090 Cov.: 32

Gnomad AFR AF: 0.953

Gnomad AMI AF: 0.873

Gnomad AMR AF: 0.794

Gnomad ASJ AF: 0.754

Gnomad EAS AF: 0.820

Gnomad SAS AF: 0.662

Gnomad FIN AF: 0.855

Gnomad MID AF: 0.687

Gnomad NFE AF: 0.817

Gnomad OTH AF: 0.814

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

GnomAD4 genome AF: 0.848 AC: 129083 AN: 152178 Hom.: 55143 Cov.: 32 AF XY: 0.846 AC XY: 62922 AN XY: 74396

African (AFR) AF: 0.954 AC: 39613 AN: 41540

American (AMR) AF: 0.794 AC: 12137 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.754 AC: 2617 AN: 3470

East Asian (EAS) AF: 0.820 AC: 4231 AN: 5160

South Asian (SAS) AF: 0.661 AC: 3183 AN: 4816

European-Finnish (FIN) AF: 0.855 AC: 9058 AN: 10594

Middle Eastern (MID) AF: 0.697 AC: 205 AN: 294

European-Non Finnish (NFE) AF: 0.817 AC: 55530 AN: 67984

Other (OTH) AF: 0.810 AC: 1713 AN: 2114

Alfa AF: 0.843 Hom.: 6735

Bravo AF: 0.849

Asia WGS AF: 0.759 AC: 2641 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.5
DANN	Benign	0.44
PhyloP100		-0.23
Mutation Taster		=300/0	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: rs3132299; hg19: chr9-137298815; COSMIC: COSV62683884; COSMIC: COSV62683884;