rs3818740

Variant names:

• chr9-134334248-T-C
• rs3818740
• NM_002957.6:c.28+7589T>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.28+7589T>C 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 152,230 control chromosomes in the GnomAD database, including 12,695 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 (12695 hom., cov: 34)
• Consequence: RXRA NM_002957.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.36
• Publications: 14 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=-0.91).
• 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+7589T>C		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+7589T>C		intron_variant	Intron 1 of 9	1	NM_002957.6	ENSP00000419692.1
RXRA	ENST00000484822.1	n.452+14764T>C		intron_variant	Intron 2 of 2	2

Frequencies

GnomAD3 genomes AF: 0.384 AC: 58383 AN: 152112 Hom.: 12664 Cov.: 34

Gnomad AFR AF: 0.592

Gnomad AMI AF: 0.225

Gnomad AMR AF: 0.376

Gnomad ASJ AF: 0.293

Gnomad EAS AF: 0.217

Gnomad SAS AF: 0.302

Gnomad FIN AF: 0.279

Gnomad MID AF: 0.348

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: 58472 AN: 152230 Hom.: 12695 Cov.: 34 AF XY: 0.380 AC XY: 28260 AN XY: 74434

African (AFR) AF: 0.593 AC: 24619 AN: 41530

American (AMR) AF: 0.376 AC: 5751 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.293 AC: 1016 AN: 3470

East Asian (EAS) AF: 0.217 AC: 1125 AN: 5184

South Asian (SAS) AF: 0.302 AC: 1461 AN: 4830

European-Finnish (FIN) AF: 0.279 AC: 2954 AN: 10598

Middle Eastern (MID) AF: 0.330 AC: 97 AN: 294

European-Non Finnish (NFE) AF: 0.301 AC: 20434 AN: 67990

Other (OTH) AF: 0.383 AC: 810 AN: 2114

Alfa AF: 0.322 Hom.: 15888

Bravo AF: 0.403

Asia WGS AF: 0.284 AC: 986 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.72
DANN	Benign	0.64
PhyloP100		-2.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs3818740; hg19: chr9-137226094;