1-165428846-C-G

Variant names:

• chr1-165428846-C-G
• ENST00000619224.1:c.-258G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001256570.2(RXRG):​c.-258G>C variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,860 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: RXRG NM_001256570.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.781

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13111678).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RXRG	NM_006917.5	c.170G>C	p.Ser57Thr	missense_variant	Exon 2 of 10	ENST00000359842.10	NP_008848.1
RXRG	NM_001256570.2	c.-258G>C		5_prime_UTR_premature_start_codon_gain_variant	Exon 2 of 11		NP_001243499.1
RXRG	NM_001256570.2	c.-258G>C		5_prime_UTR_variant	Exon 2 of 11		NP_001243499.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RXRG	ENST00000619224.1	c.-258G>C		5_prime_UTR_premature_start_codon_gain_variant	Exon 2 of 11	1		ENSP00000482458.1
RXRG	ENST00000359842.10	c.170G>C	p.Ser57Thr	missense_variant	Exon 2 of 10	1	NM_006917.5	ENSP00000352900.5
RXRG	ENST00000619224.1	c.-258G>C		5_prime_UTR_variant	Exon 2 of 11	1		ENSP00000482458.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461860 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727232

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.062
BayesDel_addAF	Benign	-0.063	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	22
DANN	Benign	0.96
DEOGEN2	Uncertain	0.42	T
Eigen	Benign	-0.31
Eigen_PC	Benign	-0.15
FATHMM_MKL	Benign	0.65	D
LIST_S2	Benign	0.63	T
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.69	T
MutationAssessor	Benign	0.78	N
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-0.68	N
REVEL	Benign	0.18
Sift	Benign	0.26	T
Sift4G	Benign	0.42	T
Polyphen		0.0030	B
Vest4		0.16
MutPred		0.16		Loss of glycosylation at S57 (P = 0.1042);
MVP		0.51
MPC		0.056
ClinPred		0.17	T
GERP RS		3.8
Varity_R		0.076
gMVP		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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-165398083;