9-134410020-A-G

Variant names:

• chr9-134410020-A-G
• rs3132297
• NM_002957.6:c.610+901A>G

Variant summary

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

The NM_002957.6(RXRA):​c.610+901A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.864 in 152,230 control chromosomes in the GnomAD database, including 57,212 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 0.86 (57212 hom., cov: 34)
• Consequence: RXRA NM_002957.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.228
• Publications: 14 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 = 0.958 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RXRA	NM_002957.6	c.610+901A>G		intron_variant	Intron 4 of 9	ENST00000481739.2	NP_002948.1
RXRA	NM_001291920.2	c.529+901A>G		intron_variant	Intron 4 of 9		NP_001278849.1
RXRA	NM_001291921.2	c.319+901A>G		intron_variant	Intron 3 of 8		NP_001278850.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RXRA	ENST00000481739.2	c.610+901A>G		intron_variant	Intron 4 of 9	1	NM_002957.6	ENSP00000419692.1
RXRA	ENST00000672570.1	c.529+901A>G		intron_variant	Intron 4 of 9			ENSP00000500402.1
RXRA	ENST00000356384.4	n.1020+901A>G		intron_variant	Intron 6 of 11	5

Frequencies

GnomAD3 genomes AF: 0.864 AC: 131408 AN: 152112 Hom.: 57160 Cov.: 34

Gnomad AFR AF: 0.966

Gnomad AMI AF: 0.928

Gnomad AMR AF: 0.819

Gnomad ASJ AF: 0.795

Gnomad EAS AF: 0.818

Gnomad SAS AF: 0.700

Gnomad FIN AF: 0.858

Gnomad MID AF: 0.699

Gnomad NFE AF: 0.832

Gnomad OTH AF: 0.836

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

GnomAD4 genome AF: 0.864 AC: 131517 AN: 152230 Hom.: 57212 Cov.: 34 AF XY: 0.862 AC XY: 64124 AN XY: 74416

African (AFR) AF: 0.966 AC: 40140 AN: 41554

American (AMR) AF: 0.818 AC: 12519 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.795 AC: 2759 AN: 3470

East Asian (EAS) AF: 0.818 AC: 4226 AN: 5164

South Asian (SAS) AF: 0.699 AC: 3373 AN: 4826

European-Finnish (FIN) AF: 0.858 AC: 9093 AN: 10598

Middle Eastern (MID) AF: 0.711 AC: 209 AN: 294

European-Non Finnish (NFE) AF: 0.832 AC: 56591 AN: 68000

Other (OTH) AF: 0.832 AC: 1761 AN: 2116

Alfa AF: 0.849 Hom.: 19172

Bravo AF: 0.866

Asia WGS AF: 0.768 AC: 2675 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	3.6
DANN	Benign	0.42
PhyloP100		-0.23
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: rs3132297; hg19: chr9-137301866;