9-134398879-G-T

Variant names:

• chr9-134398879-G-T
• rs12004589
• NM_002957.6:c.29-2753G>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.29-2753G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.129 in 152,266 control chromosomes in the GnomAD database, including 1,356 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 0.13 (1356 hom., cov: 34)
• Consequence: RXRA NM_002957.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.18
• Publications: 15 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=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.16 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.29-2753G>T		intron	N/A	NP_002948.1	P19793-1
	RXRA	NM_001291920.2		c.-53-2753G>T		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.29-2753G>T		intron	N/A	ENSP00000419692.1	P19793-1
	RXRA	ENST00000672570.1		c.-53-2753G>T		intron	N/A	ENSP00000500402.1	A0A5F9ZHH6
	RXRA	ENST00000649020.1		c.119-2753G>T		intron	N/A	ENSP00000497073.1	A0A3B3IS44

Frequencies

GnomAD3 genomes AF: 0.129 AC: 19639 AN: 152148 Hom.: 1356 Cov.: 34

Gnomad AFR AF: 0.164

Gnomad AMI AF: 0.122

Gnomad AMR AF: 0.0842

Gnomad ASJ AF: 0.0998

Gnomad EAS AF: 0.0569

Gnomad SAS AF: 0.168

Gnomad FIN AF: 0.165

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.118

Gnomad OTH AF: 0.103

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

GnomAD4 genome AF: 0.129 AC: 19646 AN: 152266 Hom.: 1356 Cov.: 34 AF XY: 0.131 AC XY: 9753 AN XY: 74472

African (AFR) AF: 0.163 AC: 6783 AN: 41530

American (AMR) AF: 0.0840 AC: 1286 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0998 AC: 346 AN: 3468

East Asian (EAS) AF: 0.0574 AC: 298 AN: 5192

South Asian (SAS) AF: 0.168 AC: 809 AN: 4828

European-Finnish (FIN) AF: 0.165 AC: 1745 AN: 10606

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.118 AC: 8024 AN: 68020

Other (OTH) AF: 0.103 AC: 218 AN: 2114

Alfa AF: 0.105 Hom.: 1102

Bravo AF: 0.122

Asia WGS AF: 0.0970 AC: 335 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.34
DANN	Benign	0.68
PhyloP100		-4.2
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: rs12004589; hg19: chr9-137290725;