rs2194899

Variant names:

• chr1-165441548-A-G
• rs2194899
• NM_006917.5:c.49+3297T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 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]

ACMG classification

Our verdict: Benign. The variant received -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.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RXRG	NM_006917.5	MANE Select	c.49+3297T>C		intron	N/A	NP_008848.1
	RXRG	NM_001256570.2		c.-379+3297T>C		intron	N/A	NP_001243499.1
	RXRG	NR_033824.2		n.282+3297T>C		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RXRG	ENST00000359842.10	TSL:1 MANE Select	c.49+3297T>C		intron	N/A	ENSP00000352900.5
	RXRG	ENST00000619224.1	TSL:1	c.-379+3297T>C		intron	N/A	ENSP00000482458.1
	RXRG	ENST00000465764.1	TSL:2	n.328+3297T>C		intron	N/A

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

African (AFR) AF: 0.287 AC: 11921 AN: 41498

American (AMR) AF: 0.485 AC: 7400 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.647 AC: 2246 AN: 3472

East Asian (EAS) AF: 0.279 AC: 1447 AN: 5178

South Asian (SAS) AF: 0.542 AC: 2611 AN: 4818

European-Finnish (FIN) AF: 0.631 AC: 6670 AN: 10568

Middle Eastern (MID) AF: 0.588 AC: 173 AN: 294

European-Non Finnish (NFE) AF: 0.636 AC: 43256 AN: 67970

Other (OTH) AF: 0.535 AC: 1132 AN: 2114

Alfa AF: 0.567 Hom.: 10215

Bravo AF: 0.486

Asia WGS AF: 0.414 AC: 1440 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.16
DANN	Benign	0.34
PhyloP100		-1.7
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: rs2194899; hg19: chr1-165410785;