9-134399894-C-T

Variant names:

• chr9-134399894-C-T
• rs35780541
• NM_002957.6:c.29-1738C>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.29-1738C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0642 in 152,232 control chromosomes in the GnomAD database, including 366 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 0.064 (366 hom., cov: 33)
• Consequence: RXRA NM_002957.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.13
• Publications: 1 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=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.144 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RXRA	NM_002957.6	c.29-1738C>T		intron_variant	Intron 1 of 9	ENST00000481739.2	NP_002948.1
RXRA	NM_001291920.2	c.-53-1738C>T		intron_variant	Intron 1 of 9		NP_001278849.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RXRA	ENST00000481739.2	c.29-1738C>T		intron_variant	Intron 1 of 9	1	NM_002957.6	ENSP00000419692.1

Frequencies

GnomAD3 genomes AF: 0.0642 AC: 9763 AN: 152114 Hom.: 366 Cov.: 33

Gnomad AFR AF: 0.0914

Gnomad AMI AF: 0.104

Gnomad AMR AF: 0.0418

Gnomad ASJ AF: 0.0366

Gnomad EAS AF: 0.0565

Gnomad SAS AF: 0.154

Gnomad FIN AF: 0.0342

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0527

Gnomad OTH AF: 0.0565

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

GnomAD4 genome AF: 0.0642 AC: 9766 AN: 152232 Hom.: 366 Cov.: 33 AF XY: 0.0648 AC XY: 4821 AN XY: 74436

African (AFR) AF: 0.0913 AC: 3792 AN: 41538

American (AMR) AF: 0.0418 AC: 639 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0366 AC: 127 AN: 3472

East Asian (EAS) AF: 0.0571 AC: 295 AN: 5170

South Asian (SAS) AF: 0.153 AC: 738 AN: 4820

European-Finnish (FIN) AF: 0.0342 AC: 363 AN: 10612

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.0526 AC: 3580 AN: 68002

Other (OTH) AF: 0.0569 AC: 120 AN: 2110

Alfa AF: 0.0522 Hom.: 268

Bravo AF: 0.0628

Asia WGS AF: 0.0870 AC: 301 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.74
DANN	Benign	0.16
PhyloP100		-1.1
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: rs35780541; hg19: chr9-137291740;