chr9-134433976-T-C

Variant names:

• chr9-134433976-T-C
• rs3132293
• NM_002957.6:c.1136-126T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 10 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=-0.93).
• 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 rank	MANE	Protein	UniProt
RXRA	NM_002957.6	c.1136-126T>C		intron_variant	Intron 8 of 9	ENST00000481739.2	NP_002948.1
RXRA	NM_001291920.2	c.1055-126T>C		intron_variant	Intron 8 of 9		NP_001278849.1
RXRA	NM_001291921.2	c.845-126T>C		intron_variant	Intron 7 of 8		NP_001278850.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RXRA	ENST00000481739.2	c.1136-126T>C		intron_variant	Intron 8 of 9	1	NM_002957.6	ENSP00000419692.1
RXRA	ENST00000672570.1	c.1055-126T>C		intron_variant	Intron 8 of 9			ENSP00000500402.1
RXRA	ENST00000356384.4	n.1546-126T>C		intron_variant	Intron 10 of 11	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

African (AFR) AF: 0.950 AC: 12933 AN: 13620

American (AMR) AF: 0.748 AC: 16122 AN: 21548

Ashkenazi Jewish (ASJ) AF: 0.746 AC: 10551 AN: 14140

East Asian (EAS) AF: 0.791 AC: 24478 AN: 30930

South Asian (SAS) AF: 0.652 AC: 31727 AN: 48624

European-Finnish (FIN) AF: 0.767 AC: 23593 AN: 30742

Middle Eastern (MID) AF: 0.708 AC: 1626 AN: 2296

European-Non Finnish (NFE) AF: 0.758 AC: 235843 AN: 311166

Other (OTH) AF: 0.771 AC: 21210 AN: 27500

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

African (AFR) AF: 0.949 AC: 39370 AN: 41500

American (AMR) AF: 0.776 AC: 11857 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.712 AC: 2472 AN: 3472

East Asian (EAS) AF: 0.816 AC: 4165 AN: 5106

South Asian (SAS) AF: 0.667 AC: 3203 AN: 4800

European-Finnish (FIN) AF: 0.764 AC: 8072 AN: 10570

Middle Eastern (MID) AF: 0.700 AC: 203 AN: 290

European-Non Finnish (NFE) AF: 0.759 AC: 51541 AN: 67886

Other (OTH) AF: 0.785 AC: 1661 AN: 2116

Alfa AF: 0.782 Hom.: 6173

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
PhyloP100		-1.2
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: rs3132293; hg19: chr9-137325822;