9-134429009-G-A

Variant names:

• chr9-134429009-G-A
• rs3118570
• NM_002957.6:c.911-99G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002957.6(RXRA):​c.911-99G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000229 in 1,309,580 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 34)
  • Exomes 𝑓: 0.0000023 (0 hom.)
• Consequence: RXRA NM_002957.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.55
• Publications: 20 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).

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.911-99G>A		intron	N/A	NP_002948.1	P19793-1
	RXRA	NM_001291920.2		c.830-99G>A		intron	N/A	NP_001278849.1	A0A5F9ZHH6
	RXRA	NM_001291921.2		c.620-99G>A		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.911-99G>A		intron	N/A	ENSP00000419692.1	P19793-1
	RXRA	ENST00000672570.1		c.830-99G>A		intron	N/A	ENSP00000500402.1	A0A5F9ZHH6
	RXRA	ENST00000356384.4	TSL:5	n.1321-99G>A		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000229 AC: 3 AN: 1309580 Hom.: 0 AF XY: 0.00000154 AC XY: 1 AN XY: 650594

African (AFR) AF: 0.00 AC: 0 AN: 30280

American (AMR) AF: 0.00 AC: 0 AN: 37850

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21654

East Asian (EAS) AF: 0.0000259 AC: 1 AN: 38648

South Asian (SAS) AF: 0.00 AC: 0 AN: 75580

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46090

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5142

European-Non Finnish (NFE) AF: 0.00000200 AC: 2 AN: 999624

Other (OTH) AF: 0.00 AC: 0 AN: 54712

GnomAD4 genome Cov.: 34

Alfa AF: 0.00 Hom.: 2952

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.7
DANN	Benign	0.94
PhyloP100		-3.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs3118570; hg19: chr9-137320855;