9-134338009-C-T

Variant names:

• chr9-134338009-C-T
• rs881658
• NM_002957.6:c.28+11350C>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.28+11350C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.384 in 152,070 control chromosomes in the GnomAD database, including 12,703 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 0.38 (12703 hom., cov: 33)
• Consequence: RXRA NM_002957.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.05
• Publications: 6 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.587 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RXRA	NM_002957.6	c.28+11350C>T		intron_variant	Intron 1 of 9	ENST00000481739.2	NP_002948.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RXRA	ENST00000481739.2	c.28+11350C>T		intron_variant	Intron 1 of 9	1	NM_002957.6	ENSP00000419692.1
RXRA	ENST00000484822.1	n.452+18525C>T		intron_variant	Intron 2 of 2	2

Frequencies

GnomAD3 genomes AF: 0.384 AC: 58333 AN: 151954 Hom.: 12669 Cov.: 33

Gnomad AFR AF: 0.593

Gnomad AMI AF: 0.224

Gnomad AMR AF: 0.376

Gnomad ASJ AF: 0.293

Gnomad EAS AF: 0.213

Gnomad SAS AF: 0.306

Gnomad FIN AF: 0.279

Gnomad MID AF: 0.350

Gnomad NFE AF: 0.301

Gnomad OTH AF: 0.380

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

GnomAD4 genome AF: 0.384 AC: 58426 AN: 152070 Hom.: 12703 Cov.: 33 AF XY: 0.380 AC XY: 28225 AN XY: 74342

African (AFR) AF: 0.593 AC: 24622 AN: 41502

American (AMR) AF: 0.375 AC: 5737 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.293 AC: 1015 AN: 3470

East Asian (EAS) AF: 0.213 AC: 1099 AN: 5162

South Asian (SAS) AF: 0.306 AC: 1471 AN: 4808

European-Finnish (FIN) AF: 0.279 AC: 2948 AN: 10572

Middle Eastern (MID) AF: 0.332 AC: 97 AN: 292

European-Non Finnish (NFE) AF: 0.301 AC: 20425 AN: 67962

Other (OTH) AF: 0.383 AC: 809 AN: 2114

Alfa AF: 0.345 Hom.: 1287

Bravo AF: 0.403

Asia WGS AF: 0.289 AC: 1002 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.72
DANN	Benign	0.84
PhyloP100		-3.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		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: rs881658; hg19: chr9-137229855;