9-134426332-C-T

Variant names:

• chr9-134426332-C-T
• rs3118571
• NM_002957.6:c.911-2776C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002957.6(RXRA):​c.911-2776C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.622 in 985,246 control chromosomes in the GnomAD database, including 196,301 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 0.52 (23179 hom., cov: 33)
  • Exomes 𝑓: 0.64 (173122 hom.)
• Consequence: RXRA NM_002957.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.677
• Publications: 21 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]

RXRA Gene-Disease associations (from GenCC):

• congenital heart disease

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.673 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002957.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RXRA	NM_002957.6	MANE Select	c.911-2776C>T		intron	N/A	NP_002948.1	P19793-1
	RXRA	NM_001291920.2		c.830-2776C>T		intron	N/A	NP_001278849.1	A0A5F9ZHH6
	RXRA	NM_001291921.2		c.620-2776C>T		intron	N/A	NP_001278850.1	P19793-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RXRA	ENST00000481739.2	TSL:1 MANE Select	c.911-2776C>T		intron	N/A	ENSP00000419692.1	P19793-1
	RXRA	ENST00000672570.1		c.830-2776C>T		intron	N/A	ENSP00000500402.1	A0A5F9ZHH6
	RXRA	ENST00000356384.4	TSL:5	n.1321-2776C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.516 AC: 78525 AN: 152040 Hom.: 23182 Cov.: 33

Gnomad AFR AF: 0.210

Gnomad AMI AF: 0.705

Gnomad AMR AF: 0.568

Gnomad ASJ AF: 0.653

Gnomad EAS AF: 0.693

Gnomad SAS AF: 0.497

Gnomad FIN AF: 0.631

Gnomad MID AF: 0.582

Gnomad NFE AF: 0.651

Gnomad OTH AF: 0.554

GnomAD4 exome AF: 0.641 AC: 533971 AN: 833086 Hom.: 173122 Cov.: 38 AF XY: 0.640 AC XY: 246333 AN XY: 384708

African (AFR) AF: 0.175 AC: 2766 AN: 15786

American (AMR) AF: 0.578 AC: 569 AN: 984

Ashkenazi Jewish (ASJ) AF: 0.667 AC: 3434 AN: 5152

East Asian (EAS) AF: 0.685 AC: 2485 AN: 3630

South Asian (SAS) AF: 0.492 AC: 8102 AN: 16460

European-Finnish (FIN) AF: 0.627 AC: 173 AN: 276

Middle Eastern (MID) AF: 0.585 AC: 948 AN: 1620

European-Non Finnish (NFE) AF: 0.654 AC: 498553 AN: 761880

Other (OTH) AF: 0.621 AC: 16941 AN: 27298

GnomAD4 genome AF: 0.516 AC: 78523 AN: 152160 Hom.: 23179 Cov.: 33 AF XY: 0.519 AC XY: 38612 AN XY: 74388

African (AFR) AF: 0.210 AC: 8704 AN: 41498

American (AMR) AF: 0.568 AC: 8687 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.653 AC: 2267 AN: 3470

East Asian (EAS) AF: 0.692 AC: 3580 AN: 5172

South Asian (SAS) AF: 0.496 AC: 2395 AN: 4824

European-Finnish (FIN) AF: 0.631 AC: 6685 AN: 10598

Middle Eastern (MID) AF: 0.588 AC: 173 AN: 294

European-Non Finnish (NFE) AF: 0.651 AC: 44232 AN: 67984

Other (OTH) AF: 0.548 AC: 1158 AN: 2114

Alfa AF: 0.606 Hom.: 50626

Bravo AF: 0.501

Asia WGS AF: 0.559 AC: 1945 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.71
DANN	Benign	0.47
PhyloP100		-0.68
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs3118571; hg19: chr9-137318178;