chr1-165401238-G-C

Position:

• chr1-165401238-G-C

Variant summary

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

The ENST00000359842.10(RXRG):​c.*25C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.182 in 1,612,480 control chromosomes in the GnomAD database, including 29,452 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 0.20 (3594 hom., cov: 32)
  • Exomes 𝑓: 0.18 (25858 hom.)
• Consequence: RXRG ENST00000359842.10 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.22

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.288 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RXRG	NM_006917.5	c.*25C>G		3_prime_UTR_variant	10/10	ENST00000359842.10	NP_008848.1
RXRG	NM_001256570.2	c.*25C>G		3_prime_UTR_variant	11/11		NP_001243499.1
RXRG	NM_001256571.2	c.*25C>G		3_prime_UTR_variant	9/9		NP_001243500.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RXRG	ENST00000359842.10	c.*25C>G		3_prime_UTR_variant	10/10	1	NM_006917.5	ENSP00000352900	P1
RXRG	ENST00000619224.1	c.*25C>G		3_prime_UTR_variant	11/11	1		ENSP00000482458

Frequencies

GnomAD3 genomes AF: 0.204 AC: 31029 AN: 151952 Hom.: 3581 Cov.: 32

Gnomad AFR AF: 0.292

Gnomad AMI AF: 0.261

Gnomad AMR AF: 0.182

Gnomad ASJ AF: 0.253

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0425

Gnomad FIN AF: 0.0987

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.196

Gnomad OTH AF: 0.213

GnomAD3 exomes AF: 0.152 AC: 38098 AN: 250328 Hom.: 3717 AF XY: 0.149 AC XY: 20155 AN XY: 135286

Gnomad AFR exome AF: 0.296

Gnomad AMR exome AF: 0.115

Gnomad ASJ exome AF: 0.248

Gnomad EAS exome AF: 0.000435

Gnomad SAS exome AF: 0.0466

Gnomad FIN exome AF: 0.101

Gnomad NFE exome AF: 0.196

Gnomad OTH exome AF: 0.168

GnomAD4 exome AF: 0.180 AC: 262341 AN: 1460410 Hom.: 25858 Cov.: 32 AF XY: 0.176 AC XY: 127831 AN XY: 726428

Gnomad4 AFR exome AF: 0.294

Gnomad4 AMR exome AF: 0.120

Gnomad4 ASJ exome AF: 0.242

Gnomad4 EAS exome AF: 0.000353

Gnomad4 SAS exome AF: 0.0463

Gnomad4 FIN exome AF: 0.109

Gnomad4 NFE exome AF: 0.197

Gnomad4 OTH exome AF: 0.184

GnomAD4 genome AF: 0.204 AC: 31069 AN: 152070 Hom.: 3594 Cov.: 32 AF XY: 0.196 AC XY: 14600 AN XY: 74358

Gnomad4 AFR AF: 0.292

Gnomad4 AMR AF: 0.182

Gnomad4 ASJ AF: 0.253

Gnomad4 EAS AF: 0.00136

Gnomad4 SAS AF: 0.0436

Gnomad4 FIN AF: 0.0987

Gnomad4 NFE AF: 0.196

Gnomad4 OTH AF: 0.212

Alfa AF: 0.202 Hom.: 595

Bravo AF: 0.217

Asia WGS AF: 0.0420 AC: 148 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.9
DANN	Benign	0.59

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: rs10918169; hg19: chr1-165370475;