9-134351537-C-T

Variant names:

• chr9-134351537-C-T
• rs11185659
• NM_002957.6:c.28+24878C>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.28+24878C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.222 in 152,264 control chromosomes in the GnomAD database, including 3,975 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 0.22 (3975 hom., cov: 33)
• Consequence: RXRA NM_002957.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00700
• Publications: 12 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.273 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RXRA	NM_002957.6	c.28+24878C>T		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+24878C>T		intron_variant	Intron 1 of 9	1	NM_002957.6	ENSP00000419692.1
RXRA	ENST00000484822.1	n.452+32053C>T		intron_variant	Intron 2 of 2	2

Frequencies

GnomAD3 genomes AF: 0.222 AC: 33744 AN: 152146 Hom.: 3967 Cov.: 33

Gnomad AFR AF: 0.277

Gnomad AMI AF: 0.173

Gnomad AMR AF: 0.183

Gnomad ASJ AF: 0.197

Gnomad EAS AF: 0.0899

Gnomad SAS AF: 0.201

Gnomad FIN AF: 0.217

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.211

Gnomad OTH AF: 0.218

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

GnomAD4 genome AF: 0.222 AC: 33783 AN: 152264 Hom.: 3975 Cov.: 33 AF XY: 0.218 AC XY: 16212 AN XY: 74456

African (AFR) AF: 0.278 AC: 11533 AN: 41536

American (AMR) AF: 0.182 AC: 2791 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.197 AC: 684 AN: 3468

East Asian (EAS) AF: 0.0897 AC: 465 AN: 5184

South Asian (SAS) AF: 0.201 AC: 972 AN: 4832

European-Finnish (FIN) AF: 0.217 AC: 2303 AN: 10610

Middle Eastern (MID) AF: 0.252 AC: 74 AN: 294

European-Non Finnish (NFE) AF: 0.211 AC: 14338 AN: 68014

Other (OTH) AF: 0.220 AC: 465 AN: 2114

Alfa AF: 0.211 Hom.: 11220

Bravo AF: 0.223

Asia WGS AF: 0.176 AC: 609 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	8.0
DANN	Benign	0.37
PhyloP100		0.0070
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: rs11185659; hg19: chr9-137243383;