9-134413069-C-T

Variant names:

• chr9-134413069-C-T
• rs3118529
• NM_002957.6:c.610+3950C>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.610+3950C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.559 in 152,042 control chromosomes in the GnomAD database, including 26,562 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 0.56 (26562 hom., cov: 34)
• Consequence: RXRA NM_002957.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.66
• Publications: 9 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.736 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.610+3950C>T		intron	N/A	NP_002948.1
	RXRA	NM_001291920.2		c.529+3950C>T		intron	N/A	NP_001278849.1
	RXRA	NM_001291921.2		c.319+3950C>T		intron	N/A	NP_001278850.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RXRA	ENST00000481739.2	TSL:1 MANE Select	c.610+3950C>T		intron	N/A	ENSP00000419692.1
	RXRA	ENST00000672570.1		c.529+3950C>T		intron	N/A	ENSP00000500402.1
	RXRA	ENST00000356384.4	TSL:5	n.1020+3950C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.560 AC: 85006 AN: 151924 Hom.: 26562 Cov.: 34

Gnomad AFR AF: 0.260

Gnomad AMI AF: 0.745

Gnomad AMR AF: 0.623

Gnomad ASJ AF: 0.671

Gnomad EAS AF: 0.756

Gnomad SAS AF: 0.518

Gnomad FIN AF: 0.691

Gnomad MID AF: 0.592

Gnomad NFE AF: 0.685

Gnomad OTH AF: 0.609

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

GnomAD4 genome AF: 0.559 AC: 85027 AN: 152042 Hom.: 26562 Cov.: 34 AF XY: 0.562 AC XY: 41753 AN XY: 74334

African (AFR) AF: 0.260 AC: 10761 AN: 41464

American (AMR) AF: 0.623 AC: 9517 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.671 AC: 2330 AN: 3472

East Asian (EAS) AF: 0.756 AC: 3885 AN: 5138

South Asian (SAS) AF: 0.518 AC: 2500 AN: 4826

European-Finnish (FIN) AF: 0.691 AC: 7326 AN: 10604

Middle Eastern (MID) AF: 0.603 AC: 176 AN: 292

European-Non Finnish (NFE) AF: 0.686 AC: 46579 AN: 67948

Other (OTH) AF: 0.603 AC: 1275 AN: 2114

Alfa AF: 0.646 Hom.: 41195

Bravo AF: 0.545

Asia WGS AF: 0.612 AC: 2131 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.54
DANN	Benign	0.74
PhyloP100		-1.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3
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: rs3118529; hg19: chr9-137304915; COSMIC: COSV62683893;