9-134433976-T-C

Position:

• chr9-134433976-T-C

Variant summary

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

The NM_002957.6(RXRA):​c.1136-126T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.768 in 652,498 control chromosomes in the GnomAD database, including 194,362 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 0.81 (50655 hom., cov: 31)
  • Exomes 𝑓: 0.76 (143707 hom.)
• Consequence: RXRA NM_002957.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.19

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.941 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RXRA	NM_002957.6	c.1136-126T>C		intron_variant		ENST00000481739.2	NP_002948.1
RXRA	NM_001291920.2	c.1055-126T>C		intron_variant			NP_001278849.1
RXRA	NM_001291921.2	c.845-126T>C		intron_variant			NP_001278850.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RXRA	ENST00000481739.2	c.1136-126T>C		intron_variant		1	NM_002957.6	ENSP00000419692	P3
RXRA	ENST00000672570.1	c.1055-126T>C		intron_variant				ENSP00000500402	A1
RXRA	ENST00000356384.4	n.1546-126T>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.812 AC: 123259 AN: 151814 Hom.: 50608 Cov.: 31

Gnomad AFR AF: 0.949

Gnomad AMI AF: 0.898

Gnomad AMR AF: 0.776

Gnomad ASJ AF: 0.712

Gnomad EAS AF: 0.816

Gnomad SAS AF: 0.669

Gnomad FIN AF: 0.764

Gnomad MID AF: 0.689

Gnomad NFE AF: 0.759

Gnomad OTH AF: 0.788

GnomAD4 exome AF: 0.755 AC: 378083 AN: 500566 Hom.: 143707 AF XY: 0.748 AC XY: 196049 AN XY: 262132

Gnomad4 AFR exome AF: 0.950

Gnomad4 AMR exome AF: 0.748

Gnomad4 ASJ exome AF: 0.746

Gnomad4 EAS exome AF: 0.791

Gnomad4 SAS exome AF: 0.652

Gnomad4 FIN exome AF: 0.767

Gnomad4 NFE exome AF: 0.758

Gnomad4 OTH exome AF: 0.771

GnomAD4 genome AF: 0.812 AC: 123361 AN: 151932 Hom.: 50655 Cov.: 31 AF XY: 0.810 AC XY: 60119 AN XY: 74250

Gnomad4 AFR AF: 0.949

Gnomad4 AMR AF: 0.776

Gnomad4 ASJ AF: 0.712

Gnomad4 EAS AF: 0.816

Gnomad4 SAS AF: 0.667

Gnomad4 FIN AF: 0.764

Gnomad4 NFE AF: 0.759

Gnomad4 OTH AF: 0.785

Alfa AF: 0.760 Hom.: 4510

Bravo AF: 0.819

Asia WGS AF: 0.755 AC: 2629 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.55
DANN	Benign	0.26

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: rs3132293; hg19: chr9-137325822;