1-165401238-G-C

Variant names:

• chr1-165401238-G-C
• rs10918169
• NM_006917.5:c.*25C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006917.5(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 NM_006917.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.22
• Publications: 13 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]

ENSG00000298458 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006917.5. 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.*25C>G		3_prime_UTR	Exon 10 of 10	NP_008848.1	P48443
	RXRG	NM_001256570.2		c.*25C>G		3_prime_UTR	Exon 11 of 11	NP_001243499.1	A0A087WZ88
	RXRG	NM_001256571.2		c.*25C>G		3_prime_UTR	Exon 9 of 9	NP_001243500.1	A0A087WZ88

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RXRG	ENST00000359842.10	TSL:1 MANE Select	c.*25C>G		3_prime_UTR	Exon 10 of 10	ENSP00000352900.5	P48443
	RXRG	ENST00000619224.1	TSL:1	c.*25C>G		3_prime_UTR	Exon 11 of 11	ENSP00000482458.1	A0A087WZ88
	RXRG	ENST00000885409.1		c.*25C>G		3_prime_UTR	Exon 10 of 10	ENSP00000555468.1

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

GnomAD2 exomes AF: 0.152 AC: 38098 AN: 250328 AF XY: 0.149

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 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

African (AFR) AF: 0.294 AC: 9838 AN: 33452

American (AMR) AF: 0.120 AC: 5368 AN: 44664

Ashkenazi Jewish (ASJ) AF: 0.242 AC: 6309 AN: 26058

East Asian (EAS) AF: 0.000353 AC: 14 AN: 39692

South Asian (SAS) AF: 0.0463 AC: 3989 AN: 86134

European-Finnish (FIN) AF: 0.109 AC: 5815 AN: 53260

Middle Eastern (MID) AF: 0.204 AC: 1158 AN: 5690

European-Non Finnish (NFE) AF: 0.197 AC: 218765 AN: 1111140

Other (OTH) AF: 0.184 AC: 11085 AN: 60320

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

African (AFR) AF: 0.292 AC: 12099 AN: 41454

American (AMR) AF: 0.182 AC: 2780 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.253 AC: 877 AN: 3470

East Asian (EAS) AF: 0.00136 AC: 7 AN: 5162

South Asian (SAS) AF: 0.0436 AC: 210 AN: 4822

European-Finnish (FIN) AF: 0.0987 AC: 1045 AN: 10586

Middle Eastern (MID) AF: 0.238 AC: 70 AN: 294

European-Non Finnish (NFE) AF: 0.196 AC: 13298 AN: 67982

Other (OTH) AF: 0.212 AC: 445 AN: 2104

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.9
DANN	Benign	0.59
PhyloP100		1.2
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: rs10918169; hg19: chr1-165370475;