9-134419554-G-A

Variant names:

• chr9-134419554-G-A
• rs4240705
• NM_002957.6:c.781-2122G>A

Variant summary

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

The NM_002957.6(RXRA):​c.781-2122G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.615 in 152,032 control chromosomes in the GnomAD database, including 28,930 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 0.62 (28930 hom., cov: 33)
• Consequence: RXRA NM_002957.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.449
• Publications: 25 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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.69 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RXRA	NM_002957.6	c.781-2122G>A		intron_variant	Intron 5 of 9	ENST00000481739.2	NP_002948.1
RXRA	NM_001291920.2	c.700-2122G>A		intron_variant	Intron 5 of 9		NP_001278849.1
RXRA	NM_001291921.2	c.490-2122G>A		intron_variant	Intron 4 of 8		NP_001278850.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RXRA	ENST00000481739.2	c.781-2122G>A		intron_variant	Intron 5 of 9	1	NM_002957.6	ENSP00000419692.1
RXRA	ENST00000672570.1	c.700-2122G>A		intron_variant	Intron 5 of 9			ENSP00000500402.1
RXRA	ENST00000356384.4	n.1191-2122G>A		intron_variant	Intron 7 of 11	5

Frequencies

GnomAD3 genomes AF: 0.616 AC: 93507 AN: 151914 Hom.: 28921 Cov.: 33

Gnomad AFR AF: 0.575

Gnomad AMI AF: 0.634

Gnomad AMR AF: 0.607

Gnomad ASJ AF: 0.629

Gnomad EAS AF: 0.709

Gnomad SAS AF: 0.520

Gnomad FIN AF: 0.643

Gnomad MID AF: 0.592

Gnomad NFE AF: 0.636

Gnomad OTH AF: 0.625

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

GnomAD4 genome AF: 0.615 AC: 93544 AN: 152032 Hom.: 28930 Cov.: 33 AF XY: 0.617 AC XY: 45855 AN XY: 74346

African (AFR) AF: 0.575 AC: 23833 AN: 41454

American (AMR) AF: 0.607 AC: 9278 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.629 AC: 2181 AN: 3470

East Asian (EAS) AF: 0.709 AC: 3644 AN: 5140

South Asian (SAS) AF: 0.519 AC: 2506 AN: 4826

European-Finnish (FIN) AF: 0.643 AC: 6813 AN: 10590

Middle Eastern (MID) AF: 0.595 AC: 175 AN: 294

European-Non Finnish (NFE) AF: 0.636 AC: 43233 AN: 67952

Other (OTH) AF: 0.619 AC: 1305 AN: 2108

Alfa AF: 0.626 Hom.: 50005

Bravo AF: 0.613

Asia WGS AF: 0.599 AC: 2085 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.0
DANN	Benign	0.91
PhyloP100		-0.45
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: rs4240705; hg19: chr9-137311400;