1-165428878-T-C

Variant names:

• chr1-165428878-T-C
• rs113471
• NM_006917.5:c.138A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 15 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: Benign. The variant received -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 rank	MANE	Protein	UniProt
RXRG	NM_006917.5	c.138A>G	p.Thr46Thr	synonymous_variant	Exon 2 of 10	ENST00000359842.10	NP_008848.1
RXRG	NM_001256570.2	c.-290A>G		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	ENST00000359842.10	c.138A>G	p.Thr46Thr	synonymous_variant	Exon 2 of 10	1	NM_006917.5	ENSP00000352900.5
RXRG	ENST00000619224.1	c.-290A>G		5_prime_UTR_variant	Exon 2 of 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

GnomAD2 exomes AF: 0.171 AC: 42920 AN: 250736 AF XY: 0.161

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 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

African (AFR) AF: 0.366 AC: 12256 AN: 33476

American (AMR) AF: 0.234 AC: 10446 AN: 44686

Ashkenazi Jewish (ASJ) AF: 0.132 AC: 3440 AN: 26128

East Asian (EAS) AF: 0.240 AC: 9506 AN: 39688

South Asian (SAS) AF: 0.106 AC: 9131 AN: 86238

European-Finnish (FIN) AF: 0.139 AC: 7407 AN: 53398

Middle Eastern (MID) AF: 0.188 AC: 1082 AN: 5768

European-Non Finnish (NFE) AF: 0.144 AC: 160407 AN: 1111832

Other (OTH) AF: 0.170 AC: 10295 AN: 60390

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

African (AFR) AF: 0.356 AC: 14755 AN: 41436

American (AMR) AF: 0.238 AC: 3642 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.127 AC: 439 AN: 3464

East Asian (EAS) AF: 0.237 AC: 1220 AN: 5158

South Asian (SAS) AF: 0.104 AC: 501 AN: 4826

European-Finnish (FIN) AF: 0.126 AC: 1336 AN: 10592

Middle Eastern (MID) AF: 0.223 AC: 65 AN: 292

European-Non Finnish (NFE) AF: 0.146 AC: 9904 AN: 67962

Other (OTH) AF: 0.209 AC: 440 AN: 2110

Alfa AF: 0.180 Hom.: 2003

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
PhyloP100		-3.7
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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