chr1-165428878-T-C

Position:

• chr1-165428878-T-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_006917.5(RXRG):​c.138A>G​(p.Thr46Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.159 in 1,613,642 control chromosomes in the GnomAD database, including 22,839 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 0.21 (4164 hom., cov: 32)
  • Exomes 𝑓: 0.15 (18675 hom.)
• Consequence: RXRG NM_006917.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.68

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BP7: Synonymous conserved (PhyloP=-3.68 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.351 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RXRG	NM_006917.5	c.138A>G	p.Thr46Thr	synonymous_variant	2/10	ENST00000359842.10	NP_008848.1
RXRG	NM_001256570.2	c.-290A>G		5_prime_UTR_variant	2/11		NP_001243499.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RXRG	ENST00000359842.10	c.138A>G	p.Thr46Thr	synonymous_variant	2/10	1	NM_006917.5	ENSP00000352900.5
RXRG	ENST00000619224.1	c.-290A>G		5_prime_UTR_variant	2/11	1		ENSP00000482458.1

Frequencies

GnomAD3 genomes AF: 0.214 AC: 32524 AN: 151920 Hom.: 4160 Cov.: 32

Gnomad AFR AF: 0.357

Gnomad AMI AF: 0.271

Gnomad AMR AF: 0.238

Gnomad ASJ AF: 0.127

Gnomad EAS AF: 0.236

Gnomad SAS AF: 0.105

Gnomad FIN AF: 0.126

Gnomad MID AF: 0.226

Gnomad NFE AF: 0.146

Gnomad OTH AF: 0.211

GnomAD3 exomes AF: 0.171 AC: 42920 AN: 250736 Hom.: 4229 AF XY: 0.161 AC XY: 21815 AN XY: 135530

Gnomad AFR exome AF: 0.361

Gnomad AMR exome AF: 0.231

Gnomad ASJ exome AF: 0.127

Gnomad EAS exome AF: 0.230

Gnomad SAS exome AF: 0.104

Gnomad FIN exome AF: 0.136

Gnomad NFE exome AF: 0.145

Gnomad OTH exome AF: 0.177

GnomAD4 exome AF: 0.153 AC: 223970 AN: 1461604 Hom.: 18675 Cov.: 33 AF XY: 0.150 AC XY: 109210 AN XY: 727114

Gnomad4 AFR exome AF: 0.366

Gnomad4 AMR exome AF: 0.234

Gnomad4 ASJ exome AF: 0.132

Gnomad4 EAS exome AF: 0.240

Gnomad4 SAS exome AF: 0.106

Gnomad4 FIN exome AF: 0.139

Gnomad4 NFE exome AF: 0.144

Gnomad4 OTH exome AF: 0.170

GnomAD4 genome AF: 0.214 AC: 32548 AN: 152038 Hom.: 4164 Cov.: 32 AF XY: 0.210 AC XY: 15610 AN XY: 74304

Gnomad4 AFR AF: 0.356

Gnomad4 AMR AF: 0.238

Gnomad4 ASJ AF: 0.127

Gnomad4 EAS AF: 0.237

Gnomad4 SAS AF: 0.104

Gnomad4 FIN AF: 0.126

Gnomad4 NFE AF: 0.146

Gnomad4 OTH AF: 0.209

Alfa AF: 0.178 Hom.: 1707

Bravo AF: 0.229

Asia WGS AF: 0.205 AC: 714 AN: 3478

EpiCase AF: 0.144

EpiControl AF: 0.146

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	1.6
DANN	Benign	0.69

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: rs113471; hg19: chr1-165398115; COSMIC: COSV63231569; COSMIC: COSV63231569;