rs10489744

Variant names:

• chr1-165411386-G-A
• rs10489744
• NM_006917.5:c.623-277C>T

Variant summary

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

The NM_006917.5(RXRG):​c.623-277C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.553 in 151,924 control chromosomes in the GnomAD database, including 25,289 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 0.55 (25289 hom., cov: 31)
• Consequence: RXRG NM_006917.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.05
• 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]

ENSG00000298458 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.667 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RXRG	NM_006917.5	MANE Select	c.623-277C>T		intron	N/A	NP_008848.1	P48443
	RXRG	NM_001256570.2		c.254-277C>T		intron	N/A	NP_001243499.1	A0A087WZ88
	RXRG	NM_001256571.2		c.254-277C>T		intron	N/A	NP_001243500.1	A0A087WZ88

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RXRG	ENST00000359842.10	TSL:1 MANE Select	c.623-277C>T		intron	N/A	ENSP00000352900.5	P48443
	RXRG	ENST00000619224.1	TSL:1	c.254-277C>T		intron	N/A	ENSP00000482458.1	A0A087WZ88
	RXRG	ENST00000885409.1		c.623-277C>T		intron	N/A	ENSP00000555468.1

Frequencies

GnomAD3 genomes AF: 0.553 AC: 83967 AN: 151806 Hom.: 25287 Cov.: 31

Gnomad AFR AF: 0.300

Gnomad AMI AF: 0.684

Gnomad AMR AF: 0.600

Gnomad ASJ AF: 0.751

Gnomad EAS AF: 0.517

Gnomad SAS AF: 0.524

Gnomad FIN AF: 0.650

Gnomad MID AF: 0.696

Gnomad NFE AF: 0.672

Gnomad OTH AF: 0.591

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

GnomAD4 genome AF: 0.553 AC: 83997 AN: 151924 Hom.: 25289 Cov.: 31 AF XY: 0.551 AC XY: 40937 AN XY: 74254

African (AFR) AF: 0.300 AC: 12417 AN: 41412

American (AMR) AF: 0.600 AC: 9168 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.751 AC: 2607 AN: 3472

East Asian (EAS) AF: 0.517 AC: 2656 AN: 5142

South Asian (SAS) AF: 0.526 AC: 2527 AN: 4806

European-Finnish (FIN) AF: 0.650 AC: 6865 AN: 10554

Middle Eastern (MID) AF: 0.690 AC: 203 AN: 294

European-Non Finnish (NFE) AF: 0.672 AC: 45688 AN: 67950

Other (OTH) AF: 0.589 AC: 1242 AN: 2108

Alfa AF: 0.584 Hom.: 21543

Bravo AF: 0.542

Asia WGS AF: 0.477 AC: 1663 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.25
DANN	Benign	0.33
PhyloP100		-1.1
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: rs10489744; hg19: chr1-165380623;