NM_002957.6:c.29-5618T>C

Variant names:

• chr9-134396014-T-C
• rs11103482
• NM_002957.6:c.29-5618T>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.29-5618T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.27 in 152,166 control chromosomes in the GnomAD database, including 9,513 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 0.27 (9513 hom., cov: 35)
• Consequence: RXRA NM_002957.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.16
• Publications: 5 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.628 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RXRA	NM_002957.6	c.29-5618T>C		intron_variant	Intron 1 of 9	ENST00000481739.2	NP_002948.1
RXRA	NM_001291920.2	c.-53-5618T>C		intron_variant	Intron 1 of 9		NP_001278849.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RXRA	ENST00000481739.2	c.29-5618T>C		intron_variant	Intron 1 of 9	1	NM_002957.6	ENSP00000419692.1

Frequencies

GnomAD3 genomes AF: 0.270 AC: 40994 AN: 152048 Hom.: 9478 Cov.: 35

Gnomad AFR AF: 0.634

Gnomad AMI AF: 0.196

Gnomad AMR AF: 0.150

Gnomad ASJ AF: 0.106

Gnomad EAS AF: 0.0558

Gnomad SAS AF: 0.178

Gnomad FIN AF: 0.167

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.125

Gnomad OTH AF: 0.212

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

GnomAD4 genome AF: 0.270 AC: 41075 AN: 152166 Hom.: 9513 Cov.: 35 AF XY: 0.266 AC XY: 19781 AN XY: 74378

African (AFR) AF: 0.635 AC: 26346 AN: 41514

American (AMR) AF: 0.150 AC: 2295 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.106 AC: 367 AN: 3472

East Asian (EAS) AF: 0.0563 AC: 290 AN: 5150

South Asian (SAS) AF: 0.178 AC: 858 AN: 4824

European-Finnish (FIN) AF: 0.167 AC: 1769 AN: 10604

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.125 AC: 8495 AN: 67994

Other (OTH) AF: 0.210 AC: 444 AN: 2110

Alfa AF: 0.200 Hom.: 2874

Bravo AF: 0.282

Asia WGS AF: 0.131 AC: 455 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	3.1
DANN	Benign	0.23
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs11103482; hg19: chr9-137287860;