rs1128977

Variant names:

• chr1-165419892-G-A
• rs1128977
• NM_006917.5:c.420C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_006917.5(RXRG):​c.420C>T​(p.Ala140Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.359 in 1,608,642 control chromosomes in the GnomAD database, including 109,519 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 0.29 (7911 hom., cov: 32)
  • Exomes 𝑓: 0.37 (101608 hom.)
• Consequence: RXRG NM_006917.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.79
• Publications: 30 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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.32).
• BP7: Synonymous conserved (PhyloP=1.79 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.385 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RXRG	NM_006917.5	c.420C>T	p.Ala140Ala	synonymous_variant	Exon 3 of 10	ENST00000359842.10	NP_008848.1
RXRG	NM_001256570.2	c.51C>T	p.Ala17Ala	synonymous_variant	Exon 4 of 11		NP_001243499.1
RXRG	NM_001256571.2	c.51C>T	p.Ala17Ala	synonymous_variant	Exon 2 of 9		NP_001243500.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RXRG	ENST00000359842.10	c.420C>T	p.Ala140Ala	synonymous_variant	Exon 3 of 10	1	NM_006917.5	ENSP00000352900.5
RXRG	ENST00000619224.1	c.51C>T	p.Ala17Ala	synonymous_variant	Exon 4 of 11	1		ENSP00000482458.1
RXRG	ENST00000470566.1	n.345C>T		non_coding_transcript_exon_variant	Exon 2 of 5	3
ENSG00000298458	ENST00000755607.1	n.514-5888G>A		intron_variant	Intron 3 of 3

Frequencies

GnomAD3 genomes AF: 0.294 AC: 44604 AN: 151914 Hom.: 7907 Cov.: 32

Gnomad AFR AF: 0.110

Gnomad AMI AF: 0.345

Gnomad AMR AF: 0.257

Gnomad ASJ AF: 0.374

Gnomad EAS AF: 0.133

Gnomad SAS AF: 0.354

Gnomad FIN AF: 0.470

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.389

Gnomad OTH AF: 0.302

GnomAD2 exomes AF: 0.337 AC: 83639 AN: 247938 AF XY: 0.349

Gnomad AFR exome AF: 0.103

Gnomad AMR exome AF: 0.245

Gnomad ASJ exome AF: 0.385

Gnomad EAS exome AF: 0.145

Gnomad FIN exome AF: 0.467

Gnomad NFE exome AF: 0.396

Gnomad OTH exome AF: 0.354

GnomAD4 exome AF: 0.366 AC: 533521 AN: 1456610 Hom.: 101608 Cov.: 34 AF XY: 0.369 AC XY: 267242 AN XY: 724616

African (AFR) AF: 0.0960 AC: 3196 AN: 33296

American (AMR) AF: 0.247 AC: 10935 AN: 44278

Ashkenazi Jewish (ASJ) AF: 0.388 AC: 10101 AN: 26038

East Asian (EAS) AF: 0.107 AC: 4228 AN: 39506

South Asian (SAS) AF: 0.356 AC: 30381 AN: 85352

European-Finnish (FIN) AF: 0.466 AC: 24840 AN: 53322

Middle Eastern (MID) AF: 0.368 AC: 2099 AN: 5700

European-Non Finnish (NFE) AF: 0.385 AC: 426808 AN: 1108910

Other (OTH) AF: 0.348 AC: 20933 AN: 60208

GnomAD4 genome AF: 0.293 AC: 44613 AN: 152032 Hom.: 7911 Cov.: 32 AF XY: 0.296 AC XY: 22015 AN XY: 74300

African (AFR) AF: 0.110 AC: 4570 AN: 41512

American (AMR) AF: 0.256 AC: 3918 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.374 AC: 1297 AN: 3464

East Asian (EAS) AF: 0.133 AC: 688 AN: 5160

South Asian (SAS) AF: 0.355 AC: 1707 AN: 4808

European-Finnish (FIN) AF: 0.470 AC: 4955 AN: 10538

Middle Eastern (MID) AF: 0.320 AC: 94 AN: 294

European-Non Finnish (NFE) AF: 0.389 AC: 26428 AN: 67958

Other (OTH) AF: 0.305 AC: 642 AN: 2106

Alfa AF: 0.355 Hom.: 46523

Bravo AF: 0.270

Asia WGS AF: 0.230 AC: 801 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.32
CADD	Benign	13
DANN	Benign	0.80
PhyloP100		1.8
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: rs1128977; hg19: chr1-165389129; COSMIC: COSV63231931;