rs283696

Positions:

• chr1-165406806-T-A
• chr1-165406806-T-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_006917.5(RXRG):​c.1244+6A>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RXRG NM_006917.5 splice_region, intron
• Scores: Splicing: ADA: 0.00008908
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.751

Genes affected

RXRG (HGNC:10479): (retinoid X receptor gamma) This gene encodes a member of the retinoid X receptor (RXR) family of nuclear receptors which are involved in mediating the antiproliferative effects of retinoic acid (RA). This receptor forms dimers with the retinoic acid, thyroid hormone, and vitamin D receptors, increasing both DNA binding and transcriptional function on their respective response elements. This gene is expressed at significantly lower levels in non-small cell lung cancer cells. Alternatively spliced transcript variants have been described. [provided by RefSeq, Jun 2010]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RXRG	NM_006917.5	c.1244+6A>T		splice_region_variant, intron_variant		ENST00000359842.10	NP_008848.1
RXRG	NM_001256570.2	c.875+6A>T		splice_region_variant, intron_variant			NP_001243499.1
RXRG	NM_001256571.2	c.875+6A>T		splice_region_variant, intron_variant			NP_001243500.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RXRG	ENST00000359842.10	c.1244+6A>T		splice_region_variant, intron_variant		1	NM_006917.5	ENSP00000352900.5
RXRG	ENST00000619224.1	c.875+6A>T		splice_region_variant, intron_variant		1		ENSP00000482458.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	3.8
DANN	Benign	0.77

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000089
dbscSNV1_RF	Benign	0.052
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: rs283696; hg19: chr1-165376043;