rs6537944

chr9-134420982-T-C

Variant summary

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

The NM_002957.6(RXRA):c.781-694T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.123 in 152,290 control chromosomes in the GnomAD database, including 1,407 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 0.12 (1407 hom., cov: 34)
• Consequence: RXRA NM_002957.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.304

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 (AFR) allele frequency at 95% confidence interval = 0.208 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RXRA	NM_002957.6	c.781-694T>C		intron_variant		ENST00000481739.2
RXRA	NM_001291920.2	c.700-694T>C		intron_variant
RXRA	NM_001291921.2	c.490-694T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RXRA	ENST00000481739.2	c.781-694T>C		intron_variant		1	NM_002957.6	P3
RXRA	ENST00000672570.1	c.700-694T>C		intron_variant				A1
RXRA	ENST00000356384.4	n.1191-694T>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.123 AC: 18718 AN: 152172 Hom.: 1400 Cov.: 34

Gnomad AFR AF: 0.212

Gnomad AMI AF: 0.161

Gnomad AMR AF: 0.103

Gnomad ASJ AF: 0.0600

Gnomad EAS AF: 0.132

Gnomad SAS AF: 0.136

Gnomad FIN AF: 0.0932

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0796

Gnomad OTH AF: 0.119

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

GnomAD4 genome AF: 0.123 AC: 18753 AN: 152290 Hom.: 1407 Cov.: 34 AF XY: 0.122 AC XY: 9091 AN XY: 74446

Gnomad4 AFR AF: 0.212

Gnomad4 AMR AF: 0.103

Gnomad4 ASJ AF: 0.0600

Gnomad4 EAS AF: 0.132

Gnomad4 SAS AF: 0.136

Gnomad4 FIN AF: 0.0932

Gnomad4 NFE AF: 0.0796

Gnomad4 OTH AF: 0.119

Alfa AF: 0.0871 Hom.: 632

Bravo AF: 0.126

Asia WGS AF: 0.145 AC: 502 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	0.85
Dann	Benign	0.50

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: rs6537944; hg19: chr9-137312828;