1-165425645-T-C

Variant names:

• chr1-165425645-T-C
• rs466639
• NM_006917.5:c.297+3074A>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.297+3074A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.874 in 152,222 control chromosomes in the GnomAD database, including 58,180 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 0.87 (58180 hom., cov: 33)
• Consequence: RXRG NM_006917.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.181
• Publications: 44 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.91 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RXRG	NM_006917.5	c.297+3074A>G		intron_variant	Intron 2 of 9	ENST00000359842.10	NP_008848.1
RXRG	NM_001256570.2	c.-130-837A>G		intron_variant	Intron 2 of 10		NP_001243499.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RXRG	ENST00000359842.10	c.297+3074A>G		intron_variant	Intron 2 of 9	1	NM_006917.5	ENSP00000352900.5
RXRG	ENST00000619224.1	c.-130-837A>G		intron_variant	Intron 2 of 10	1		ENSP00000482458.1
ENSG00000298458	ENST00000755607.1	n.514-135T>C		intron_variant	Intron 3 of 3

Frequencies

GnomAD3 genomes AF: 0.874 AC: 132891 AN: 152104 Hom.: 58137 Cov.: 33

Gnomad AFR AF: 0.863

Gnomad AMI AF: 0.862

Gnomad AMR AF: 0.922

Gnomad ASJ AF: 0.906

Gnomad EAS AF: 0.858

Gnomad SAS AF: 0.783

Gnomad FIN AF: 0.842

Gnomad MID AF: 0.915

Gnomad NFE AF: 0.879

Gnomad OTH AF: 0.892

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

GnomAD4 genome AF: 0.874 AC: 132992 AN: 152222 Hom.: 58180 Cov.: 33 AF XY: 0.871 AC XY: 64814 AN XY: 74418

African (AFR) AF: 0.863 AC: 35840 AN: 41518

American (AMR) AF: 0.923 AC: 14122 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.906 AC: 3146 AN: 3472

East Asian (EAS) AF: 0.858 AC: 4446 AN: 5184

South Asian (SAS) AF: 0.784 AC: 3777 AN: 4818

European-Finnish (FIN) AF: 0.842 AC: 8923 AN: 10600

Middle Eastern (MID) AF: 0.915 AC: 269 AN: 294

European-Non Finnish (NFE) AF: 0.879 AC: 59802 AN: 68006

Other (OTH) AF: 0.891 AC: 1881 AN: 2112

Alfa AF: 0.878 Hom.: 236555

Bravo AF: 0.880

Asia WGS AF: 0.832 AC: 2892 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	4.8
DANN	Benign	0.72
PhyloP100		-0.18
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: rs466639; hg19: chr1-165394882;