rs11185644

Variant names:

• chr9-134319017-T-C
• rs11185644
• ENST00000484822.1:n.406-421T>C

Your query was ambiguous. Multiple possible variants found:

• chr9-134319017-T-C
• chr9-134319017-T-G

Variant summary

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

The ENST00000484822.1(RXRA):​n.406-421T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.273 in 152,200 control chromosomes in the GnomAD database, including 7,828 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as drug response (no stars).

• Frequency: Genomes: 𝑓 0.27 (7828 hom., cov: 33)
• Consequence: RXRA ENST00000484822.1 intron
• Clinical Significance: drug response no assertion criteria provided O:1
• Conservation: PhyloP100: -3.36
• Publications: 17 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]

RXRA Gene-Disease associations (from GenCC):

• congenital heart disease

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.521 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000484822.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RXRA	ENST00000484822.1	TSL:2	n.406-421T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.273 AC: 41444 AN: 152082 Hom.: 7817 Cov.: 33

Gnomad AFR AF: 0.527

Gnomad AMI AF: 0.105

Gnomad AMR AF: 0.301

Gnomad ASJ AF: 0.209

Gnomad EAS AF: 0.0673

Gnomad SAS AF: 0.0776

Gnomad FIN AF: 0.112

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.171

Gnomad OTH AF: 0.272

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

GnomAD4 genome AF: 0.273 AC: 41501 AN: 152200 Hom.: 7828 Cov.: 33 AF XY: 0.266 AC XY: 19789 AN XY: 74410

African (AFR) AF: 0.527 AC: 21879 AN: 41516

American (AMR) AF: 0.301 AC: 4607 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.209 AC: 726 AN: 3470

East Asian (EAS) AF: 0.0669 AC: 346 AN: 5174

South Asian (SAS) AF: 0.0778 AC: 376 AN: 4830

European-Finnish (FIN) AF: 0.112 AC: 1192 AN: 10600

Middle Eastern (MID) AF: 0.221 AC: 65 AN: 294

European-Non Finnish (NFE) AF: 0.171 AC: 11632 AN: 67998

Other (OTH) AF: 0.275 AC: 582 AN: 2114

Alfa AF: 0.205 Hom.: 5310

Bravo AF: 0.303

Asia WGS AF: 0.105 AC: 365 AN: 3478

ClinVar

ClinVar submissions

Significance: drug response

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	-	Levothyroxine response (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.016
DANN	Benign	0.54
PhyloP100		-3.4

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs11185644; hg19: chr9-137210863;