9-134396900-T-C

Variant names:

• chr9-134396900-T-C
• rs10776909
• NM_002957.6:c.29-4732T>C

Variant summary

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

The NM_002957.6(RXRA):​c.29-4732T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.822 in 152,228 control chromosomes in the GnomAD database, including 51,829 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 0.82 (51829 hom., cov: 33)
• Consequence: RXRA NM_002957.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.27
• Publications: 28 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 = 0.918 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.29-4732T>C		intron	N/A	NP_002948.1	P19793-1
	RXRA	NM_001291920.2		c.-53-4732T>C		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.29-4732T>C		intron	N/A	ENSP00000419692.1	P19793-1
	RXRA	ENST00000672570.1		c.-53-4732T>C		intron	N/A	ENSP00000500402.1	A0A5F9ZHH6
	RXRA	ENST00000649020.1		c.119-4732T>C		intron	N/A	ENSP00000497073.1	A0A3B3IS44

Frequencies

GnomAD3 genomes AF: 0.822 AC: 125082 AN: 152110 Hom.: 51786 Cov.: 33

Gnomad AFR AF: 0.926

Gnomad AMI AF: 0.864

Gnomad AMR AF: 0.759

Gnomad ASJ AF: 0.731

Gnomad EAS AF: 0.796

Gnomad SAS AF: 0.660

Gnomad FIN AF: 0.808

Gnomad MID AF: 0.690

Gnomad NFE AF: 0.794

Gnomad OTH AF: 0.802

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

GnomAD4 genome AF: 0.822 AC: 125184 AN: 152228 Hom.: 51829 Cov.: 33 AF XY: 0.819 AC XY: 60957 AN XY: 74440

African (AFR) AF: 0.926 AC: 38477 AN: 41544

American (AMR) AF: 0.759 AC: 11618 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.731 AC: 2538 AN: 3472

East Asian (EAS) AF: 0.796 AC: 4106 AN: 5156

South Asian (SAS) AF: 0.659 AC: 3176 AN: 4822

European-Finnish (FIN) AF: 0.808 AC: 8581 AN: 10620

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

European-Non Finnish (NFE) AF: 0.794 AC: 54008 AN: 67994

Other (OTH) AF: 0.799 AC: 1689 AN: 2114

Alfa AF: 0.789 Hom.: 38374

Bravo AF: 0.824

Asia WGS AF: 0.737 AC: 2565 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	1.3
DANN	Benign	0.48
PhyloP100		-2.3
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: rs10776909; hg19: chr9-137288746; COSMIC: COSV62683862;