ENST00000619224.1:c.-217C>G

Variant names:

• chr1-165428805-G-C
• rs1469851984
• ENST00000619224.1:c.-217C>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The ENST00000619224.1(RXRG):​c.-217C>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: RXRG ENST00000619224.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.106
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000619224.1. 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
	RXRG	NM_006917.5	MANE Select	c.211C>G	p.Arg71Gly	missense	Exon 2 of 10	NP_008848.1	P48443
	RXRG	NM_001256570.2		c.-217C>G		5_prime_UTR_premature_start_codon_gain	Exon 2 of 11	NP_001243499.1	A0A087WZ88
	RXRG	NM_001256570.2		c.-217C>G		5_prime_UTR	Exon 2 of 11	NP_001243499.1	A0A087WZ88

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RXRG	ENST00000619224.1	TSL:1	c.-217C>G		5_prime_UTR_premature_start_codon_gain	Exon 2 of 11	ENSP00000482458.1	A0A087WZ88
	RXRG	ENST00000359842.10	TSL:1 MANE Select	c.211C>G	p.Arg71Gly	missense	Exon 2 of 10	ENSP00000352900.5	P48443
	RXRG	ENST00000619224.1	TSL:1	c.-217C>G		5_prime_UTR	Exon 2 of 11	ENSP00000482458.1	A0A087WZ88

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
PhyloP100		0.11
Varity_R		0.11
gMVP		0.44
Mutation Taster		=90/10	polymorphism

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1469851984; hg19: chr1-165398042; COSMIC: COSV100717262; COSMIC: COSV100717262;