9-134393657-A-G

Variant names:

• chr9-134393657-A-G
• rs11102986
• NM_002957.6:c.29-7975A>G

Variant summary

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

The NM_002957.6(RXRA):​c.29-7975A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.852 in 152,250 control chromosomes in the GnomAD database, including 55,649 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 (55649 hom., cov: 33)
• Consequence: RXRA NM_002957.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.831
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.944 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.29-7975A>G		intron	N/A	NP_002948.1	P19793-1
	RXRA	NM_001291920.2		c.-53-7975A>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.29-7975A>G		intron	N/A	ENSP00000419692.1	P19793-1
	RXRA	ENST00000672570.1		c.-53-7975A>G		intron	N/A	ENSP00000500402.1	A0A5F9ZHH6
	RXRA	ENST00000649020.1		c.118+7267A>G		intron	N/A	ENSP00000497073.1	A0A3B3IS44

Frequencies

GnomAD3 genomes AF: 0.852 AC: 129662 AN: 152132 Hom.: 55596 Cov.: 33

Gnomad AFR AF: 0.951

Gnomad AMI AF: 0.874

Gnomad AMR AF: 0.785

Gnomad ASJ AF: 0.785

Gnomad EAS AF: 0.856

Gnomad SAS AF: 0.707

Gnomad FIN AF: 0.845

Gnomad MID AF: 0.712

Gnomad NFE AF: 0.823

Gnomad OTH AF: 0.834

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

GnomAD4 genome AF: 0.852 AC: 129772 AN: 152250 Hom.: 55649 Cov.: 33 AF XY: 0.850 AC XY: 63246 AN XY: 74442

African (AFR) AF: 0.951 AC: 39540 AN: 41560

American (AMR) AF: 0.785 AC: 11998 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.785 AC: 2725 AN: 3472

East Asian (EAS) AF: 0.857 AC: 4438 AN: 5178

South Asian (SAS) AF: 0.706 AC: 3408 AN: 4824

European-Finnish (FIN) AF: 0.845 AC: 8973 AN: 10614

Middle Eastern (MID) AF: 0.718 AC: 211 AN: 294

European-Non Finnish (NFE) AF: 0.823 AC: 55925 AN: 67990

Other (OTH) AF: 0.831 AC: 1757 AN: 2114

Alfa AF: 0.824 Hom.: 171816

Bravo AF: 0.853

Asia WGS AF: 0.787 AC: 2739 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	6.3
DANN	Benign	0.76
PhyloP100		0.83
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

Other links and lift over

dbSNP: rs11102986; hg19: chr9-137285503; COSMIC: COSV62683851;