NM_002957.6:c.1135+810A>G

Variant names:

• chr9-134432806-A-G
• rs749759
• NM_002957.6:c.1135+810A>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.1135+810A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.811 in 152,104 control chromosomes in the GnomAD database, including 50,579 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 (50579 hom., cov: 32)
• Consequence: RXRA NM_002957.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0370
• Publications: 16 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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.939 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RXRA	NM_002957.6	c.1135+810A>G		intron_variant	Intron 8 of 9	ENST00000481739.2	NP_002948.1
RXRA	NM_001291920.2	c.1054+810A>G		intron_variant	Intron 8 of 9		NP_001278849.1
RXRA	NM_001291921.2	c.844+810A>G		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.1135+810A>G		intron_variant	Intron 8 of 9	1	NM_002957.6	ENSP00000419692.1
RXRA	ENST00000672570.1	c.1054+810A>G		intron_variant	Intron 8 of 9			ENSP00000500402.1
RXRA	ENST00000356384.4	n.1545+810A>G		intron_variant	Intron 10 of 11	5

Frequencies

GnomAD3 genomes AF: 0.811 AC: 123241 AN: 151986 Hom.: 50534 Cov.: 32

Gnomad AFR AF: 0.947

Gnomad AMI AF: 0.898

Gnomad AMR AF: 0.775

Gnomad ASJ AF: 0.712

Gnomad EAS AF: 0.815

Gnomad SAS AF: 0.663

Gnomad FIN AF: 0.763

Gnomad MID AF: 0.687

Gnomad NFE AF: 0.759

Gnomad OTH AF: 0.788

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

GnomAD4 genome AF: 0.811 AC: 123341 AN: 152104 Hom.: 50579 Cov.: 32 AF XY: 0.809 AC XY: 60108 AN XY: 74342

African (AFR) AF: 0.947 AC: 39330 AN: 41542

American (AMR) AF: 0.775 AC: 11859 AN: 15294

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

East Asian (EAS) AF: 0.815 AC: 4177 AN: 5128

South Asian (SAS) AF: 0.661 AC: 3185 AN: 4818

European-Finnish (FIN) AF: 0.763 AC: 8069 AN: 10572

Middle Eastern (MID) AF: 0.697 AC: 205 AN: 294

European-Non Finnish (NFE) AF: 0.759 AC: 51571 AN: 67964

Other (OTH) AF: 0.785 AC: 1656 AN: 2110

Alfa AF: 0.793 Hom.: 5952

Bravo AF: 0.818

Asia WGS AF: 0.755 AC: 2626 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.97
DANN	Benign	0.27
PhyloP100		-0.037
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: rs749759; hg19: chr9-137324652; COSMIC: COSV62683915;