chr9-134416616-A-C

Variant names:

• chr9-134416616-A-C
• rs3118536
• NM_002957.6:c.611-542A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002957.6(RXRA):​c.611-542A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.864 in 151,988 control chromosomes in the GnomAD database, including 57,156 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 0.86 (57156 hom., cov: 30)
• Consequence: RXRA NM_002957.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.92
• Publications: 29 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.958 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RXRA	NM_002957.6	c.611-542A>C		intron_variant	Intron 4 of 9	ENST00000481739.2	NP_002948.1
RXRA	NM_001291920.2	c.530-542A>C		intron_variant	Intron 4 of 9		NP_001278849.1
RXRA	NM_001291921.2	c.320-542A>C		intron_variant	Intron 3 of 8		NP_001278850.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RXRA	ENST00000481739.2	c.611-542A>C		intron_variant	Intron 4 of 9	1	NM_002957.6	ENSP00000419692.1
RXRA	ENST00000672570.1	c.530-542A>C		intron_variant	Intron 4 of 9			ENSP00000500402.1
RXRA	ENST00000356384.4	n.1021-542A>C		intron_variant	Intron 6 of 11	5

Frequencies

GnomAD3 genomes AF: 0.864 AC: 131240 AN: 151870 Hom.: 57103 Cov.: 30

Gnomad AFR AF: 0.966

Gnomad AMI AF: 0.902

Gnomad AMR AF: 0.819

Gnomad ASJ AF: 0.796

Gnomad EAS AF: 0.814

Gnomad SAS AF: 0.705

Gnomad FIN AF: 0.859

Gnomad MID AF: 0.699

Gnomad NFE AF: 0.833

Gnomad OTH AF: 0.838

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

GnomAD4 genome AF: 0.864 AC: 131349 AN: 151988 Hom.: 57156 Cov.: 30 AF XY: 0.862 AC XY: 64039 AN XY: 74294

African (AFR) AF: 0.966 AC: 40084 AN: 41490

American (AMR) AF: 0.819 AC: 12515 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.796 AC: 2763 AN: 3472

East Asian (EAS) AF: 0.814 AC: 4164 AN: 5116

South Asian (SAS) AF: 0.703 AC: 3380 AN: 4806

European-Finnish (FIN) AF: 0.859 AC: 9088 AN: 10584

Middle Eastern (MID) AF: 0.711 AC: 209 AN: 294

European-Non Finnish (NFE) AF: 0.833 AC: 56571 AN: 67926

Other (OTH) AF: 0.834 AC: 1756 AN: 2106

Alfa AF: 0.830 Hom.: 122219

Bravo AF: 0.866

Asia WGS AF: 0.768 AC: 2673 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.57
DANN	Benign	0.69
PhyloP100		-2.9
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: rs3118536; hg19: chr9-137308462; COSMIC: COSV62685242;