9-134340689-A-G

Position:

• chr9-134340689-A-G

Variant summary

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

The NM_002957.6(RXRA):​c.28+14030A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.315 in 152,096 control chromosomes in the GnomAD database, including 7,751 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 0.31 (7751 hom., cov: 32)
• Consequence: RXRA NM_002957.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.30

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.377 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RXRA	NM_002957.6	c.28+14030A>G		intron_variant		ENST00000481739.2	NP_002948.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RXRA	ENST00000481739.2	c.28+14030A>G		intron_variant		1	NM_002957.6	ENSP00000419692	P3
RXRA	ENST00000484822.1	n.452+21205A>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.315 AC: 47802 AN: 151978 Hom.: 7741 Cov.: 32

Gnomad AFR AF: 0.382

Gnomad AMI AF: 0.222

Gnomad AMR AF: 0.341

Gnomad ASJ AF: 0.282

Gnomad EAS AF: 0.215

Gnomad SAS AF: 0.297

Gnomad FIN AF: 0.275

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.285

Gnomad OTH AF: 0.333

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

GnomAD4 genome AF: 0.315 AC: 47852 AN: 152096 Hom.: 7751 Cov.: 32 AF XY: 0.313 AC XY: 23250 AN XY: 74376

Gnomad4 AFR AF: 0.382

Gnomad4 AMR AF: 0.341

Gnomad4 ASJ AF: 0.282

Gnomad4 EAS AF: 0.216

Gnomad4 SAS AF: 0.297

Gnomad4 FIN AF: 0.275

Gnomad4 NFE AF: 0.285

Gnomad4 OTH AF: 0.333

Alfa AF: 0.305 Hom.: 5286

Bravo AF: 0.325

Asia WGS AF: 0.268 AC: 929 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.80
DANN	Benign	0.34

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs10881578; hg19: chr9-137232535;