1-165414524-C-T

Variant names:

• chr1-165414524-C-T
• rs157864
• NM_006917.5:c.622+2517G>A

Variant summary

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

The NM_006917.5(RXRG):​c.622+2517G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.148 in 152,224 control chromosomes in the GnomAD database, including 1,733 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 0.15 (1733 hom., cov: 33)
• Consequence: RXRG NM_006917.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0260

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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.223 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RXRG	NM_006917.5	c.622+2517G>A		intron_variant	Intron 4 of 9	ENST00000359842.10	NP_008848.1
RXRG	NM_001256570.2	c.253+2517G>A		intron_variant	Intron 5 of 10		NP_001243499.1
RXRG	NM_001256571.2	c.253+2517G>A		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.622+2517G>A		intron_variant	Intron 4 of 9	1	NM_006917.5	ENSP00000352900.5
RXRG	ENST00000619224.1	c.253+2517G>A		intron_variant	Intron 5 of 10	1		ENSP00000482458.1
RXRG	ENST00000470566.1	n.547+2517G>A		intron_variant	Intron 3 of 4	3

Frequencies

GnomAD3 genomes AF: 0.148 AC: 22570 AN: 152104 Hom.: 1731 Cov.: 33

Gnomad AFR AF: 0.126

Gnomad AMI AF: 0.141

Gnomad AMR AF: 0.122

Gnomad ASJ AF: 0.118

Gnomad EAS AF: 0.216

Gnomad SAS AF: 0.235

Gnomad FIN AF: 0.177

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.154

Gnomad OTH AF: 0.137

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

GnomAD4 genome AF: 0.148 AC: 22586 AN: 152224 Hom.: 1733 Cov.: 33 AF XY: 0.152 AC XY: 11281 AN XY: 74428

Gnomad4 AFR AF: 0.126

Gnomad4 AMR AF: 0.122

Gnomad4 ASJ AF: 0.118

Gnomad4 EAS AF: 0.216

Gnomad4 SAS AF: 0.234

Gnomad4 FIN AF: 0.177

Gnomad4 NFE AF: 0.154

Gnomad4 OTH AF: 0.138

Alfa AF: 0.154 Hom.: 879

Bravo AF: 0.142

Asia WGS AF: 0.211 AC: 733 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.2
DANN	Benign	0.68

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: rs157864; hg19: chr1-165383761;