chr9-134356320-T-C

Variant names:

• chr9-134356320-T-C
• rs7864987
• NM_002957.6:c.28+29661T>C

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+29661T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.333 in 151,974 control chromosomes in the GnomAD database, including 10,311 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 0.33 (10311 hom., cov: 32)
• Consequence: RXRA NM_002957.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.62
• Publications: 11 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]

RXRA Gene-Disease associations (from GenCC):

• congenital heart disease

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: ClinGen

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 (AFR) allele frequency at 95% confidence interval = 0.571 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002957.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RXRA	NM_002957.6	MANE Select	c.28+29661T>C		intron	N/A	NP_002948.1	P19793-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RXRA	ENST00000481739.2	TSL:1 MANE Select	c.28+29661T>C		intron	N/A	ENSP00000419692.1	P19793-1
	RXRA	ENST00000484822.1	TSL:2	n.452+36836T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.333 AC: 50546 AN: 151856 Hom.: 10276 Cov.: 32

Gnomad AFR AF: 0.576

Gnomad AMI AF: 0.214

Gnomad AMR AF: 0.240

Gnomad ASJ AF: 0.220

Gnomad EAS AF: 0.146

Gnomad SAS AF: 0.272

Gnomad FIN AF: 0.219

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.250

Gnomad OTH AF: 0.307

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

GnomAD4 genome AF: 0.333 AC: 50637 AN: 151974 Hom.: 10311 Cov.: 32 AF XY: 0.326 AC XY: 24221 AN XY: 74304

African (AFR) AF: 0.577 AC: 23903 AN: 41434

American (AMR) AF: 0.240 AC: 3663 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.220 AC: 762 AN: 3466

East Asian (EAS) AF: 0.147 AC: 756 AN: 5158

South Asian (SAS) AF: 0.271 AC: 1304 AN: 4812

European-Finnish (FIN) AF: 0.219 AC: 2316 AN: 10562

Middle Eastern (MID) AF: 0.269 AC: 79 AN: 294

European-Non Finnish (NFE) AF: 0.250 AC: 17005 AN: 67952

Other (OTH) AF: 0.310 AC: 654 AN: 2110

Alfa AF: 0.280 Hom.: 1646

Bravo AF: 0.345

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.0
DANN	Benign	0.49
PhyloP100		-1.6
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs7864987; hg19: chr9-137248166;