9-134368146-T-C

Variant names:

• chr9-134368146-T-C
• rs11185660
• NM_002957.6:c.29-33486T>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.29-33486T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.29 in 152,160 control chromosomes in the GnomAD database, including 6,899 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 0.29 (6899 hom., cov: 34)
• Consequence: RXRA NM_002957.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.01
• Publications: 7 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.395 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.29-33486T>C		intron	N/A	NP_002948.1	P19793-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RXRA	ENST00000481739.2	TSL:1 MANE Select	c.29-33486T>C		intron	N/A	ENSP00000419692.1	P19793-1
	RXRA	ENST00000484822.1	TSL:2	n.453-33486T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.290 AC: 44131 AN: 152042 Hom.: 6886 Cov.: 34

Gnomad AFR AF: 0.400

Gnomad AMI AF: 0.183

Gnomad AMR AF: 0.340

Gnomad ASJ AF: 0.271

Gnomad EAS AF: 0.187

Gnomad SAS AF: 0.226

Gnomad FIN AF: 0.243

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.235

Gnomad OTH AF: 0.287

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

GnomAD4 genome AF: 0.290 AC: 44202 AN: 152160 Hom.: 6899 Cov.: 34 AF XY: 0.288 AC XY: 21418 AN XY: 74374

African (AFR) AF: 0.400 AC: 16602 AN: 41510

American (AMR) AF: 0.340 AC: 5201 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.271 AC: 940 AN: 3472

East Asian (EAS) AF: 0.186 AC: 963 AN: 5166

South Asian (SAS) AF: 0.226 AC: 1093 AN: 4828

European-Finnish (FIN) AF: 0.243 AC: 2577 AN: 10600

Middle Eastern (MID) AF: 0.327 AC: 96 AN: 294

European-Non Finnish (NFE) AF: 0.235 AC: 15946 AN: 67960

Other (OTH) AF: 0.292 AC: 617 AN: 2114

Alfa AF: 0.256 Hom.: 7520

Bravo AF: 0.307

Asia WGS AF: 0.237 AC: 822 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.8
DANN	Benign	0.68
PhyloP100		-1.0
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: rs11185660; hg19: chr9-137259992;