rs875444

chr9-134403458-G-Achr9-134403458-G-Cchr9-134403458-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002957.6(RXRA):c.279+1576G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.467 in 152,234 control chromosomes in the GnomAD database, including 19,346 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 0.47 (19334 hom., cov: 35)
  • Exomes 𝑓: 0.58 (12 hom.)
• Consequence: RXRA NM_002957.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.305

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.599 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RXRA	NM_002957.6	c.279+1576G>A		intron_variant		ENST00000481739.2
RXRA	NM_001291920.2	c.198+1576G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RXRA	ENST00000481739.2	c.279+1576G>A		intron_variant		1	NM_002957.6	P3
RXRA	ENST00000672570.1	c.198+1576G>A		intron_variant				A1
RXRA	ENST00000484822.1	n.2279G>A		non_coding_transcript_exon_variant	3/3	2
RXRA	ENST00000356384.4	n.689+1576G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.467 AC: 71030 AN: 152056 Hom.: 19337 Cov.: 35

Gnomad AFR AF: 0.169

Gnomad AMI AF: 0.607

Gnomad AMR AF: 0.514

Gnomad ASJ AF: 0.573

Gnomad EAS AF: 0.599

Gnomad SAS AF: 0.436

Gnomad FIN AF: 0.582

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.604

Gnomad OTH AF: 0.504

GnomAD4 exome AF: 0.583 AC: 35 AN: 60 Hom.: 12 Cov.: 0 AF XY: 0.605 AC XY: 23 AN XY: 38

Gnomad4 AFR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.500

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.750

Gnomad4 NFE exome AF: 0.643

Gnomad4 OTH exome AF: 0.667

GnomAD4 genome AF: 0.467 AC: 71019 AN: 152174 Hom.: 19334 Cov.: 35 AF XY: 0.467 AC XY: 34778 AN XY: 74392

Gnomad4 AFR AF: 0.168

Gnomad4 AMR AF: 0.515

Gnomad4 ASJ AF: 0.573

Gnomad4 EAS AF: 0.598

Gnomad4 SAS AF: 0.436

Gnomad4 FIN AF: 0.582

Gnomad4 NFE AF: 0.604

Gnomad4 OTH AF: 0.500

Alfa AF: 0.568 Hom.: 22117

Bravo AF: 0.452

Asia WGS AF: 0.496 AC: 1726 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	2.1
Dann	Benign	0.68

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

Publications

LitVar

Other links and lift over

dbSNP: rs875444; hg19: chr9-137295304;