rs2134095

Variant names:

• chr1-165408315-G-A
• rs2134095
• NM_006917.5:c.1050C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-165408315-G-A
• chr1-165408315-G-C
• chr1-165408315-G-T

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.1050C>T​(p.Val350Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.636 in 1,603,440 control chromosomes in the GnomAD database, including 332,343 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 0.55 (25289 hom., cov: 32)
  • Exomes 𝑓: 0.65 (307054 hom.)
• Consequence: RXRG NM_006917.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.918
• Publications: 39 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP7: Synonymous conserved (PhyloP=-0.918 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.667 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RXRG	NM_006917.5	c.1050C>T	p.Val350Val	synonymous_variant	Exon 8 of 10	ENST00000359842.10	NP_008848.1
RXRG	NM_001256570.2	c.681C>T	p.Val227Val	synonymous_variant	Exon 9 of 11		NP_001243499.1
RXRG	NM_001256571.2	c.681C>T	p.Val227Val	synonymous_variant	Exon 7 of 9		NP_001243500.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RXRG	ENST00000359842.10	c.1050C>T	p.Val350Val	synonymous_variant	Exon 8 of 10	1	NM_006917.5	ENSP00000352900.5
RXRG	ENST00000619224.1	c.681C>T	p.Val227Val	synonymous_variant	Exon 9 of 11	1		ENSP00000482458.1
ENSG00000298458	ENST00000755607.1	n.513+16115G>A		intron_variant	Intron 3 of 3

Frequencies

GnomAD3 genomes AF: 0.553 AC: 83971 AN: 151860 Hom.: 25287 Cov.: 32

Gnomad AFR AF: 0.300

Gnomad AMI AF: 0.684

Gnomad AMR AF: 0.601

Gnomad ASJ AF: 0.752

Gnomad EAS AF: 0.513

Gnomad SAS AF: 0.525

Gnomad FIN AF: 0.650

Gnomad MID AF: 0.696

Gnomad NFE AF: 0.672

Gnomad OTH AF: 0.592

GnomAD2 exomes AF: 0.614 AC: 154447 AN: 251362 AF XY: 0.619

Gnomad AFR exome AF: 0.286

Gnomad AMR exome AF: 0.608

Gnomad ASJ exome AF: 0.764

Gnomad EAS exome AF: 0.534

Gnomad FIN exome AF: 0.645

Gnomad NFE exome AF: 0.679

Gnomad OTH exome AF: 0.640

GnomAD4 exome AF: 0.645 AC: 936335 AN: 1451462 Hom.: 307054 Cov.: 30 AF XY: 0.645 AC XY: 465982 AN XY: 722886

African (AFR) AF: 0.283 AC: 9454 AN: 33354

American (AMR) AF: 0.605 AC: 27062 AN: 44698

Ashkenazi Jewish (ASJ) AF: 0.758 AC: 19761 AN: 26078

East Asian (EAS) AF: 0.465 AC: 18457 AN: 39652

South Asian (SAS) AF: 0.531 AC: 45651 AN: 86050

European-Finnish (FIN) AF: 0.653 AC: 34849 AN: 53402

Middle Eastern (MID) AF: 0.678 AC: 3893 AN: 5744

European-Non Finnish (NFE) AF: 0.671 AC: 739269 AN: 1102394

Other (OTH) AF: 0.631 AC: 37939 AN: 60090

GnomAD4 genome AF: 0.553 AC: 84000 AN: 151978 Hom.: 25289 Cov.: 32 AF XY: 0.551 AC XY: 40957 AN XY: 74302

African (AFR) AF: 0.299 AC: 12395 AN: 41404

American (AMR) AF: 0.601 AC: 9186 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.752 AC: 2608 AN: 3466

East Asian (EAS) AF: 0.513 AC: 2652 AN: 5172

South Asian (SAS) AF: 0.527 AC: 2536 AN: 4814

European-Finnish (FIN) AF: 0.650 AC: 6860 AN: 10560

Middle Eastern (MID) AF: 0.690 AC: 203 AN: 294

European-Non Finnish (NFE) AF: 0.672 AC: 45696 AN: 67962

Other (OTH) AF: 0.590 AC: 1243 AN: 2106

Alfa AF: 0.635 Hom.: 136021

Bravo AF: 0.542

EpiCase AF: 0.686

EpiControl AF: 0.690

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	3.3
DANN	Benign	0.60
PhyloP100		-0.92
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: rs2134095; hg19: chr1-165377552; COSMIC: COSV63231656; COSMIC: COSV63231656;