rs11381416

Variant names:

• chr9-134432215-G-GA
• rs11381416
• NM_002957.6:c.1135+220dupA

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_002957.6(RXRA):​c.1135+220dupA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0554 in 152,272 control chromosomes in the GnomAD database, including 326 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.055 (326 hom., cov: 33)
• Consequence: RXRA NM_002957.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.18
• Publications: 3 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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0784 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RXRA	NM_002957.6	c.1135+220dupA		intron_variant	Intron 8 of 9	ENST00000481739.2	NP_002948.1
RXRA	NM_001291920.2	c.1054+220dupA		intron_variant	Intron 8 of 9		NP_001278849.1
RXRA	NM_001291921.2	c.844+220dupA		intron_variant	Intron 7 of 8		NP_001278850.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RXRA	ENST00000481739.2	c.1135+219_1135+220insA		intron_variant	Intron 8 of 9	1	NM_002957.6	ENSP00000419692.1
RXRA	ENST00000672570.1	c.1054+219_1054+220insA		intron_variant	Intron 8 of 9			ENSP00000500402.1
RXRA	ENST00000356384.4	n.1545+219_1545+220insA		intron_variant	Intron 10 of 11	5

Frequencies

GnomAD3 genomes AF: 0.0555 AC: 8450 AN: 152154 Hom.: 327 Cov.: 33

Gnomad AFR AF: 0.0145

Gnomad AMI AF: 0.0571

Gnomad AMR AF: 0.0529

Gnomad ASJ AF: 0.102

Gnomad EAS AF: 0.000962

Gnomad SAS AF: 0.0326

Gnomad FIN AF: 0.0773

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.0801

Gnomad OTH AF: 0.0702

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

GnomAD4 genome AF: 0.0554 AC: 8442 AN: 152272 Hom.: 326 Cov.: 33 AF XY: 0.0541 AC XY: 4031 AN XY: 74450

African (AFR) AF: 0.0145 AC: 602 AN: 41576

American (AMR) AF: 0.0529 AC: 809 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.102 AC: 355 AN: 3472

East Asian (EAS) AF: 0.000579 AC: 3 AN: 5184

South Asian (SAS) AF: 0.0331 AC: 159 AN: 4808

European-Finnish (FIN) AF: 0.0773 AC: 820 AN: 10612

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.0801 AC: 5450 AN: 67998

Other (OTH) AF: 0.0690 AC: 146 AN: 2116

Alfa AF: 0.0211 Hom.: 4

Bravo AF: 0.0532

Asia WGS AF: 0.0130 AC: 46 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-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: rs11381416; hg19: chr9-137324061;