rs2194899

chr1-165441548-A-G

Variant summary

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

The NM_006917.5(RXRG):c.49+3297T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.508 in 152,094 control chromosomes in the GnomAD database, including 21,556 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 0.51 (21556 hom., cov: 33)
• Consequence: RXRG NM_006917.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.72

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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.631 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RXRG	NM_006917.5	c.49+3297T>C		intron_variant		ENST00000359842.10
RXRG	NM_001256570.2	c.-379+3297T>C		intron_variant
RXRG	NR_033824.2	n.282+3297T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RXRG	ENST00000359842.10	c.49+3297T>C		intron_variant		1	NM_006917.5	P1
RXRG	ENST00000619224.1	c.-379+3297T>C		intron_variant		1
RXRG	ENST00000465764.1	n.328+3297T>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.508 AC: 77202 AN: 151976 Hom.: 21547 Cov.: 33

Gnomad AFR AF: 0.287

Gnomad AMI AF: 0.421

Gnomad AMR AF: 0.485

Gnomad ASJ AF: 0.647

Gnomad EAS AF: 0.279

Gnomad SAS AF: 0.540

Gnomad FIN AF: 0.631

Gnomad MID AF: 0.592

Gnomad NFE AF: 0.636

Gnomad OTH AF: 0.532

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

GnomAD4 genome AF: 0.508 AC: 77239 AN: 152094 Hom.: 21556 Cov.: 33 AF XY: 0.507 AC XY: 37669 AN XY: 74340

Gnomad4 AFR AF: 0.287

Gnomad4 AMR AF: 0.485

Gnomad4 ASJ AF: 0.647

Gnomad4 EAS AF: 0.279

Gnomad4 SAS AF: 0.542

Gnomad4 FIN AF: 0.631

Gnomad4 NFE AF: 0.636

Gnomad4 OTH AF: 0.535

Alfa AF: 0.568 Hom.: 6568

Bravo AF: 0.486

Asia WGS AF: 0.414 AC: 1440 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.16
Dann	Benign	0.34

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: rs2194899; hg19: chr1-165410785;