rs877954

Variant names:

• chr9-134434562-A-G
• rs877954
• NM_002957.6:c.1241+355A>G

Variant summary

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

The NM_002957.6(RXRA):​c.1241+355A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.548 in 152,114 control chromosomes in the GnomAD database, including 24,778 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 0.55 (24778 hom., cov: 34)
• Consequence: RXRA NM_002957.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.958
• Publications: 22 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.655 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RXRA	NM_002957.6	c.1241+355A>G		intron_variant	Intron 9 of 9	ENST00000481739.2	NP_002948.1
RXRA	NM_001291920.2	c.1160+355A>G		intron_variant	Intron 9 of 9		NP_001278849.1
RXRA	NM_001291921.2	c.950+355A>G		intron_variant	Intron 8 of 8		NP_001278850.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RXRA	ENST00000481739.2	c.1241+355A>G		intron_variant	Intron 9 of 9	1	NM_002957.6	ENSP00000419692.1
RXRA	ENST00000672570.1	c.1160+355A>G		intron_variant	Intron 9 of 9			ENSP00000500402.1
RXRA	ENST00000356384.4	n.1651+355A>G		intron_variant	Intron 11 of 11	5

Frequencies

GnomAD3 genomes AF: 0.549 AC: 83382 AN: 151996 Hom.: 24779 Cov.: 34

Gnomad AFR AF: 0.306

Gnomad AMI AF: 0.719

Gnomad AMR AF: 0.585

Gnomad ASJ AF: 0.646

Gnomad EAS AF: 0.654

Gnomad SAS AF: 0.501

Gnomad FIN AF: 0.647

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.660

Gnomad OTH AF: 0.579

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

GnomAD4 genome AF: 0.548 AC: 83390 AN: 152114 Hom.: 24778 Cov.: 34 AF XY: 0.550 AC XY: 40904 AN XY: 74350

African (AFR) AF: 0.305 AC: 12668 AN: 41478

American (AMR) AF: 0.586 AC: 8954 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.646 AC: 2238 AN: 3466

East Asian (EAS) AF: 0.654 AC: 3363 AN: 5144

South Asian (SAS) AF: 0.500 AC: 2411 AN: 4826

European-Finnish (FIN) AF: 0.647 AC: 6851 AN: 10588

Middle Eastern (MID) AF: 0.565 AC: 166 AN: 294

European-Non Finnish (NFE) AF: 0.660 AC: 44871 AN: 67998

Other (OTH) AF: 0.573 AC: 1212 AN: 2116

Alfa AF: 0.623 Hom.: 50579

Bravo AF: 0.537

Asia WGS AF: 0.565 AC: 1966 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	0.29
DANN	Benign	0.43
PhyloP100		-0.96
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: rs877954; hg19: chr9-137326408; COSMIC: COSV62683919;