9-134413069-C-T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RXRA	NM_002957.6	c.610+3950C>T		intron_variant		ENST00000481739.2
RXRA	NM_001291920.2	c.529+3950C>T		intron_variant
RXRA	NM_001291921.2	c.319+3950C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RXRA	ENST00000481739.2	c.610+3950C>T		intron_variant		1	NM_002957.6	P3
RXRA	ENST00000672570.1	c.529+3950C>T		intron_variant				A1
RXRA	ENST00000356384.4	n.1020+3950C>T		intron_variant, non_coding_transcript_variant		5

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

Gnomad4 AFR AF: 0.260

Gnomad4 AMR AF: 0.623

Gnomad4 ASJ AF: 0.671

Gnomad4 EAS AF: 0.756

Gnomad4 SAS AF: 0.518

Gnomad4 FIN AF: 0.691

Gnomad4 NFE AF: 0.686

Gnomad4 OTH AF: 0.603

Alfa AF: 0.661 Hom.: 32786

Bravo AF: 0.545

Asia WGS AF: 0.612 AC: 2131 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	0.54
Dann	Benign	0.74
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs3118529; hg19: chr9-137304915; COSMIC: COSV62683893;