chr9-134417615-C-T

Variant names:

• chr9-134417615-C-T
• rs7861779
• NM_002957.6:c.780+288C>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.780+288C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.271 in 151,834 control chromosomes in the GnomAD database, including 8,718 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 0.27 (8718 hom., cov: 31)
• Consequence: RXRA NM_002957.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.44
• 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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.586 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RXRA	NM_002957.6	MANE Select	c.780+288C>T		intron	N/A	NP_002948.1
	RXRA	NM_001291920.2		c.699+288C>T		intron	N/A	NP_001278849.1
	RXRA	NM_001291921.2		c.489+288C>T		intron	N/A	NP_001278850.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RXRA	ENST00000481739.2	TSL:1 MANE Select	c.780+288C>T		intron	N/A	ENSP00000419692.1
	RXRA	ENST00000672570.1		c.699+288C>T		intron	N/A	ENSP00000500402.1
	RXRA	ENST00000356384.4	TSL:5	n.1190+288C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.271 AC: 41084 AN: 151716 Hom.: 8687 Cov.: 31

Gnomad AFR AF: 0.591

Gnomad AMI AF: 0.222

Gnomad AMR AF: 0.185

Gnomad ASJ AF: 0.123

Gnomad EAS AF: 0.0556

Gnomad SAS AF: 0.180

Gnomad FIN AF: 0.162

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.146

Gnomad OTH AF: 0.205

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

GnomAD4 genome AF: 0.271 AC: 41165 AN: 151834 Hom.: 8718 Cov.: 31 AF XY: 0.268 AC XY: 19873 AN XY: 74206

African (AFR) AF: 0.592 AC: 24437 AN: 41294

American (AMR) AF: 0.185 AC: 2826 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.123 AC: 426 AN: 3470

East Asian (EAS) AF: 0.0559 AC: 288 AN: 5150

South Asian (SAS) AF: 0.179 AC: 862 AN: 4812

European-Finnish (FIN) AF: 0.162 AC: 1715 AN: 10598

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.146 AC: 9946 AN: 67918

Other (OTH) AF: 0.207 AC: 438 AN: 2112

Alfa AF: 0.372 Hom.: 3061

Bravo AF: 0.285

Asia WGS AF: 0.144 AC: 502 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.54
DANN	Benign	0.50
PhyloP100		-2.4
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs7861779; hg19: chr9-137309461;