rs285480

chr1-165434666-G-Achr1-165434666-G-Cchr1-165434666-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006917.5(RXRG):c.50-5700C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.728 in 152,098 control chromosomes in the GnomAD database, including 40,702 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 0.73 (40702 hom., cov: 32)
• Consequence: RXRG NM_006917.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.35

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.811 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RXRG	NM_006917.5	c.50-5700C>T		intron_variant		ENST00000359842.10
RXRG	NM_001256570.2	c.-378-5700C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RXRG	ENST00000359842.10	c.50-5700C>T		intron_variant		1	NM_006917.5	P1
RXRG	ENST00000619224.1	c.-378-5700C>T		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.728 AC: 110670 AN: 151980 Hom.: 40691 Cov.: 32

Gnomad AFR AF: 0.617

Gnomad AMI AF: 0.799

Gnomad AMR AF: 0.777

Gnomad ASJ AF: 0.854

Gnomad EAS AF: 0.832

Gnomad SAS AF: 0.692

Gnomad FIN AF: 0.719

Gnomad MID AF: 0.880

Gnomad NFE AF: 0.772

Gnomad OTH AF: 0.764

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.728 AC: 110732 AN: 152098 Hom.: 40702 Cov.: 32 AF XY: 0.726 AC XY: 53982 AN XY: 74344

Gnomad4 AFR AF: 0.617

Gnomad4 AMR AF: 0.776

Gnomad4 ASJ AF: 0.854

Gnomad4 EAS AF: 0.832

Gnomad4 SAS AF: 0.693

Gnomad4 FIN AF: 0.719

Gnomad4 NFE AF: 0.772

Gnomad4 OTH AF: 0.764

Alfa AF: 0.775 Hom.: 100590

Bravo AF: 0.730

Asia WGS AF: 0.758 AC: 2638 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.33
Dann	Benign	0.39

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: rs285480; hg19: chr1-165403903;