9-134338170-A-G

Variant names:

• chr9-134338170-A-G
• rs881657
• NM_002957.6:c.28+11511A>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.28+11511A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.377 in 151,768 control chromosomes in the GnomAD database, including 11,979 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 0.38 (11979 hom., cov: 34)
• Consequence: RXRA NM_002957.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0350
• Publications: 7 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.563 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RXRA	NM_002957.6	c.28+11511A>G		intron_variant	Intron 1 of 9	ENST00000481739.2	NP_002948.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RXRA	ENST00000481739.2	c.28+11511A>G		intron_variant	Intron 1 of 9	1	NM_002957.6	ENSP00000419692.1
RXRA	ENST00000484822.1	n.452+18686A>G		intron_variant	Intron 2 of 2	2

Frequencies

GnomAD3 genomes AF: 0.377 AC: 57125 AN: 151650 Hom.: 11954 Cov.: 34

Gnomad AFR AF: 0.569

Gnomad AMI AF: 0.223

Gnomad AMR AF: 0.373

Gnomad ASJ AF: 0.292

Gnomad EAS AF: 0.215

Gnomad SAS AF: 0.307

Gnomad FIN AF: 0.277

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.300

Gnomad OTH AF: 0.377

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

GnomAD4 genome AF: 0.377 AC: 57205 AN: 151768 Hom.: 11979 Cov.: 34 AF XY: 0.373 AC XY: 27668 AN XY: 74166

African (AFR) AF: 0.570 AC: 23546 AN: 41340

American (AMR) AF: 0.372 AC: 5685 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.292 AC: 1011 AN: 3464

East Asian (EAS) AF: 0.215 AC: 1104 AN: 5132

South Asian (SAS) AF: 0.307 AC: 1479 AN: 4822

European-Finnish (FIN) AF: 0.277 AC: 2924 AN: 10556

Middle Eastern (MID) AF: 0.333 AC: 98 AN: 294

European-Non Finnish (NFE) AF: 0.300 AC: 20353 AN: 67874

Other (OTH) AF: 0.380 AC: 802 AN: 2108

Alfa AF: 0.353 Hom.: 1354

Bravo AF: 0.396

Asia WGS AF: 0.286 AC: 992 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	3.6
DANN	Benign	0.35
PhyloP100		-0.035
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: rs881657; hg19: chr9-137230016;