rs2651860

Variant names:

• chr1-165411818-A-C
• rs2651860
• NM_006917.5:c.623-709T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006917.5(RXRG):​c.623-709T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.174 in 152,108 control chromosomes in the GnomAD database, including 2,447 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 0.17 (2447 hom., cov: 32)
• Consequence: RXRG NM_006917.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.513
• Publications: 7 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.2 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RXRG	NM_006917.5	c.623-709T>G		intron_variant	Intron 4 of 9	ENST00000359842.10	NP_008848.1
RXRG	NM_001256570.2	c.254-709T>G		intron_variant	Intron 5 of 10		NP_001243499.1
RXRG	NM_001256571.2	c.254-709T>G		intron_variant	Intron 3 of 8		NP_001243500.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RXRG	ENST00000359842.10	c.623-709T>G		intron_variant	Intron 4 of 9	1	NM_006917.5	ENSP00000352900.5
RXRG	ENST00000619224.1	c.254-709T>G		intron_variant	Intron 5 of 10	1		ENSP00000482458.1
RXRG	ENST00000470566.1	n.548-709T>G		intron_variant	Intron 3 of 4	3
ENSG00000298458	ENST00000755607.1	n.514-13962A>C		intron_variant	Intron 3 of 3

Frequencies

GnomAD3 genomes AF: 0.174 AC: 26430 AN: 151990 Hom.: 2447 Cov.: 32

Gnomad AFR AF: 0.127

Gnomad AMI AF: 0.236

Gnomad AMR AF: 0.173

Gnomad ASJ AF: 0.147

Gnomad EAS AF: 0.115

Gnomad SAS AF: 0.190

Gnomad FIN AF: 0.198

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.202

Gnomad OTH AF: 0.187

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

GnomAD4 genome AF: 0.174 AC: 26435 AN: 152108 Hom.: 2447 Cov.: 32 AF XY: 0.174 AC XY: 12970 AN XY: 74348

African (AFR) AF: 0.127 AC: 5284 AN: 41508

American (AMR) AF: 0.173 AC: 2643 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.147 AC: 512 AN: 3472

East Asian (EAS) AF: 0.115 AC: 594 AN: 5168

South Asian (SAS) AF: 0.190 AC: 912 AN: 4812

European-Finnish (FIN) AF: 0.198 AC: 2089 AN: 10574

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.202 AC: 13756 AN: 67974

Other (OTH) AF: 0.186 AC: 393 AN: 2112

Alfa AF: 0.194 Hom.: 5835

Bravo AF: 0.171

Asia WGS AF: 0.159 AC: 552 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.7
DANN	Benign	0.51
PhyloP100		0.51
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: rs2651860; hg19: chr1-165381055;