rs6537944

Variant names:

• chr9-134420982-T-C
• rs6537944
• NM_002957.6:c.781-694T>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.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
• Publications: 18 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=-0.9).
• 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 rank	MANE	Protein	UniProt
RXRA	NM_002957.6	c.781-694T>C		intron_variant	Intron 5 of 9	ENST00000481739.2	NP_002948.1
RXRA	NM_001291920.2	c.700-694T>C		intron_variant	Intron 5 of 9		NP_001278849.1
RXRA	NM_001291921.2	c.490-694T>C		intron_variant	Intron 4 of 8		NP_001278850.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RXRA	ENST00000481739.2	c.781-694T>C		intron_variant	Intron 5 of 9	1	NM_002957.6	ENSP00000419692.1
RXRA	ENST00000672570.1	c.700-694T>C		intron_variant	Intron 5 of 9			ENSP00000500402.1
RXRA	ENST00000356384.4	n.1191-694T>C		intron_variant	Intron 7 of 11	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

African (AFR) AF: 0.212 AC: 8799 AN: 41550

American (AMR) AF: 0.103 AC: 1575 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.0600 AC: 208 AN: 3468

East Asian (EAS) AF: 0.132 AC: 686 AN: 5178

South Asian (SAS) AF: 0.136 AC: 656 AN: 4832

European-Finnish (FIN) AF: 0.0932 AC: 989 AN: 10614

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.0796 AC: 5413 AN: 68020

Other (OTH) AF: 0.119 AC: 252 AN: 2114

Alfa AF: 0.0939 Hom.: 1359

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
PhyloP100		-0.30
Mutation Taster		=99/1	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: rs6537944; hg19: chr9-137312828;