chr9-134337481-A-G

Variant names:

• chr9-134337481-A-G
• rs12339187
• NM_002957.6:c.28+10822A>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.28+10822A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.18 in 152,082 control chromosomes in the GnomAD database, including 2,560 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 0.18 (2560 hom., cov: 33)
• Consequence: RXRA NM_002957.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00600
• Publications: 15 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 = 0.197 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RXRA	NM_002957.6	c.28+10822A>G		intron_variant	Intron 1 of 9	ENST00000481739.2	NP_002948.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RXRA	ENST00000481739.2	c.28+10822A>G		intron_variant	Intron 1 of 9	1	NM_002957.6	ENSP00000419692.1
RXRA	ENST00000484822.1	n.452+17997A>G		intron_variant	Intron 2 of 2	2

Frequencies

GnomAD3 genomes AF: 0.180 AC: 27411 AN: 151962 Hom.: 2557 Cov.: 33

Gnomad AFR AF: 0.200

Gnomad AMI AF: 0.173

Gnomad AMR AF: 0.160

Gnomad ASJ AF: 0.183

Gnomad EAS AF: 0.0928

Gnomad SAS AF: 0.196

Gnomad FIN AF: 0.200

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.175

Gnomad OTH AF: 0.185

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

GnomAD4 genome AF: 0.180 AC: 27436 AN: 152082 Hom.: 2560 Cov.: 33 AF XY: 0.179 AC XY: 13334 AN XY: 74332

African (AFR) AF: 0.200 AC: 8309 AN: 41476

American (AMR) AF: 0.159 AC: 2436 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.183 AC: 635 AN: 3472

East Asian (EAS) AF: 0.0926 AC: 477 AN: 5152

South Asian (SAS) AF: 0.196 AC: 944 AN: 4824

European-Finnish (FIN) AF: 0.200 AC: 2122 AN: 10584

Middle Eastern (MID) AF: 0.228 AC: 67 AN: 294

European-Non Finnish (NFE) AF: 0.175 AC: 11895 AN: 67972

Other (OTH) AF: 0.187 AC: 394 AN: 2108

Alfa AF: 0.176 Hom.: 6042

Bravo AF: 0.178

Asia WGS AF: 0.155 AC: 537 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	3.5
DANN	Benign	0.55
PhyloP100		0.0060
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: rs12339187; hg19: chr9-137229327;