9-134410785-C-T

Variant names:

• chr9-134410785-C-T
• rs3132296
• NM_002957.6:c.610+1666C>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.610+1666C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.589 in 152,090 control chromosomes in the GnomAD database, including 27,971 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 0.59 (27971 hom., cov: 34)
• Consequence: RXRA NM_002957.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.355
• 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]

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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.736 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.610+1666C>T		intron	N/A	NP_002948.1	P19793-1
	RXRA	NM_001291920.2		c.529+1666C>T		intron	N/A	NP_001278849.1	A0A5F9ZHH6
	RXRA	NM_001291921.2		c.319+1666C>T		intron	N/A	NP_001278850.1	P19793-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RXRA	ENST00000481739.2	TSL:1 MANE Select	c.610+1666C>T		intron	N/A	ENSP00000419692.1	P19793-1
	RXRA	ENST00000672570.1		c.529+1666C>T		intron	N/A	ENSP00000500402.1	A0A5F9ZHH6
	RXRA	ENST00000356384.4	TSL:5	n.1020+1666C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.590 AC: 89602 AN: 151972 Hom.: 27969 Cov.: 34

Gnomad AFR AF: 0.371

Gnomad AMI AF: 0.682

Gnomad AMR AF: 0.631

Gnomad ASJ AF: 0.671

Gnomad EAS AF: 0.756

Gnomad SAS AF: 0.517

Gnomad FIN AF: 0.690

Gnomad MID AF: 0.604

Gnomad NFE AF: 0.684

Gnomad OTH AF: 0.629

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

GnomAD4 genome AF: 0.589 AC: 89630 AN: 152090 Hom.: 27971 Cov.: 34 AF XY: 0.590 AC XY: 43878 AN XY: 74344

African (AFR) AF: 0.371 AC: 15371 AN: 41478

American (AMR) AF: 0.631 AC: 9648 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.671 AC: 2331 AN: 3472

East Asian (EAS) AF: 0.756 AC: 3904 AN: 5162

South Asian (SAS) AF: 0.516 AC: 2489 AN: 4820

European-Finnish (FIN) AF: 0.690 AC: 7307 AN: 10592

Middle Eastern (MID) AF: 0.616 AC: 181 AN: 294

European-Non Finnish (NFE) AF: 0.684 AC: 46465 AN: 67962

Other (OTH) AF: 0.623 AC: 1315 AN: 2112

Alfa AF: 0.654 Hom.: 53601

Bravo AF: 0.579

Asia WGS AF: 0.618 AC: 2152 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.30
DANN	Benign	0.75
PhyloP100		-0.35
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
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: rs3132296; hg19: chr9-137302631;