1-165408924-C-G

Position:

• chr1-165408924-C-G

Variant summary

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

The NM_006917.5(RXRG):​c.1047-606G>C 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 152,142 control chromosomes in the GnomAD database, including 2,452 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 (2452 hom., cov: 32)
• Consequence: RXRG NM_006917.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.547

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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.199 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RXRG	NM_006917.5	c.1047-606G>C		intron_variant		ENST00000359842.10	NP_008848.1
RXRG	NM_001256570.2	c.678-606G>C		intron_variant			NP_001243499.1
RXRG	NM_001256571.2	c.678-606G>C		intron_variant			NP_001243500.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RXRG	ENST00000359842.10	c.1047-606G>C		intron_variant		1	NM_006917.5	ENSP00000352900.5
RXRG	ENST00000619224.1	c.678-606G>C		intron_variant		1		ENSP00000482458.1

Frequencies

GnomAD3 genomes AF: 0.175 AC: 26531 AN: 152024 Hom.: 2452 Cov.: 32

Gnomad AFR AF: 0.132

Gnomad AMI AF: 0.236

Gnomad AMR AF: 0.172

Gnomad ASJ AF: 0.146

Gnomad EAS AF: 0.119

Gnomad SAS AF: 0.172

Gnomad FIN AF: 0.199

Gnomad MID AF: 0.121

Gnomad NFE AF: 0.202

Gnomad OTH AF: 0.184

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

GnomAD4 genome AF: 0.174 AC: 26537 AN: 152142 Hom.: 2452 Cov.: 32 AF XY: 0.175 AC XY: 12996 AN XY: 74372

Gnomad4 AFR AF: 0.132

Gnomad4 AMR AF: 0.172

Gnomad4 ASJ AF: 0.146

Gnomad4 EAS AF: 0.119

Gnomad4 SAS AF: 0.172

Gnomad4 FIN AF: 0.199

Gnomad4 NFE AF: 0.202

Gnomad4 OTH AF: 0.184

Alfa AF: 0.101 Hom.: 166

Bravo AF: 0.172

Asia WGS AF: 0.148 AC: 512 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.99
DANN	Benign	0.43

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: rs157861; hg19: chr1-165378161;