chr9-134345449-T-A

Variant names:

• chr9-134345449-T-A
• rs4917353
• NM_002957.6:c.28+18790T>A

Variant summary

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

The ENST00000481739.2(RXRA):​c.28+18790T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.418 in 152,046 control chromosomes in the GnomAD database, including 15,906 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 0.42 (15906 hom., cov: 32)
• Consequence: RXRA ENST00000481739.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.201
• Publications: 6 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.701 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000481739.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RXRA	NM_002957.6	MANE Select	c.28+18790T>A		intron	N/A	NP_002948.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RXRA	ENST00000481739.2	TSL:1 MANE Select	c.28+18790T>A		intron	N/A	ENSP00000419692.1
	RXRA	ENST00000484822.1	TSL:2	n.452+25965T>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.417 AC: 63384 AN: 151928 Hom.: 15863 Cov.: 32

Gnomad AFR AF: 0.707

Gnomad AMI AF: 0.226

Gnomad AMR AF: 0.387

Gnomad ASJ AF: 0.292

Gnomad EAS AF: 0.215

Gnomad SAS AF: 0.312

Gnomad FIN AF: 0.279

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.302

Gnomad OTH AF: 0.402

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

GnomAD4 genome AF: 0.418 AC: 63489 AN: 152046 Hom.: 15906 Cov.: 32 AF XY: 0.411 AC XY: 30561 AN XY: 74322

African (AFR) AF: 0.708 AC: 29360 AN: 41498

American (AMR) AF: 0.387 AC: 5907 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.292 AC: 1013 AN: 3470

East Asian (EAS) AF: 0.215 AC: 1109 AN: 5154

South Asian (SAS) AF: 0.312 AC: 1500 AN: 4812

European-Finnish (FIN) AF: 0.279 AC: 2947 AN: 10568

Middle Eastern (MID) AF: 0.333 AC: 98 AN: 294

European-Non Finnish (NFE) AF: 0.302 AC: 20494 AN: 67954

Other (OTH) AF: 0.404 AC: 855 AN: 2114

Alfa AF: 0.353 Hom.: 1343

Bravo AF: 0.440

Asia WGS AF: 0.301 AC: 1044 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	2.1
DANN	Benign	0.57
PhyloP100		-0.20
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		2.2
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: rs4917353; hg19: chr9-137237295;