9-134429009-G-T

Variant names:

• chr9-134429009-G-T
• rs3118570
• NM_002957.6:c.911-99G>T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002957.6(RXRA):​c.911-99G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.822 in 1,460,516 control chromosomes in the GnomAD database, including 495,853 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 0.86 (56440 hom., cov: 34)
  • Exomes 𝑓: 0.82 (439413 hom.)
• Consequence: RXRA NM_002957.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.55

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.956 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RXRA	NM_002957.6	c.911-99G>T		intron_variant	Intron 6 of 9	ENST00000481739.2	NP_002948.1
RXRA	NM_001291920.2	c.830-99G>T		intron_variant	Intron 6 of 9		NP_001278849.1
RXRA	NM_001291921.2	c.620-99G>T		intron_variant	Intron 5 of 8		NP_001278850.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RXRA	ENST00000481739.2	c.911-99G>T		intron_variant	Intron 6 of 9	1	NM_002957.6	ENSP00000419692.1
RXRA	ENST00000672570.1	c.830-99G>T		intron_variant	Intron 6 of 9			ENSP00000500402.1
RXRA	ENST00000356384.4	n.1321-99G>T		intron_variant	Intron 8 of 11	5

Frequencies

GnomAD3 genomes AF: 0.858 AC: 130502 AN: 152138 Hom.: 56386 Cov.: 34

Gnomad AFR AF: 0.963

Gnomad AMI AF: 0.909

Gnomad AMR AF: 0.812

Gnomad ASJ AF: 0.775

Gnomad EAS AF: 0.809

Gnomad SAS AF: 0.688

Gnomad FIN AF: 0.857

Gnomad MID AF: 0.693

Gnomad NFE AF: 0.825

Gnomad OTH AF: 0.826

GnomAD4 exome AF: 0.818 AC: 1070498 AN: 1308260 Hom.: 439413 AF XY: 0.813 AC XY: 528335 AN XY: 649980

Gnomad4 AFR exome AF: 0.968

Gnomad4 AMR exome AF: 0.761

Gnomad4 ASJ exome AF: 0.797

Gnomad4 EAS exome AF: 0.781

Gnomad4 SAS exome AF: 0.672

Gnomad4 FIN exome AF: 0.850

Gnomad4 NFE exome AF: 0.828

Gnomad4 OTH exome AF: 0.815

GnomAD4 genome AF: 0.858 AC: 130611 AN: 152256 Hom.: 56440 Cov.: 34 AF XY: 0.856 AC XY: 63721 AN XY: 74424

Gnomad4 AFR AF: 0.963

Gnomad4 AMR AF: 0.812

Gnomad4 ASJ AF: 0.775

Gnomad4 EAS AF: 0.809

Gnomad4 SAS AF: 0.686

Gnomad4 FIN AF: 0.857

Gnomad4 NFE AF: 0.825

Gnomad4 OTH AF: 0.822

Alfa AF: 0.822 Hom.: 2952

Bravo AF: 0.859

Asia WGS AF: 0.754 AC: 2623 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.24
DANN	Benign	0.65
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs3118570; hg19: chr9-137320855; COSMIC: COSV62683906;