chr1-165406806-T-C

Variant names:

• chr1-165406806-T-C
• rs283696
• NM_006917.5:c.1244+6A>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.1244+6A>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.806 in 1,608,144 control chromosomes in the GnomAD database, including 524,306 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.82 (51796 hom., cov: 32)
  • Exomes 𝑓: 0.80 (472510 hom.)
• Consequence: RXRG NM_006917.5 splice_region, intron
• Scores: Splicing: ADA: 0.0001361
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.751
• Publications: 17 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=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.905 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RXRG	NM_006917.5	c.1244+6A>G		splice_region_variant, intron_variant	Intron 9 of 9	ENST00000359842.10	NP_008848.1
RXRG	NM_001256570.2	c.875+6A>G		splice_region_variant, intron_variant	Intron 10 of 10		NP_001243499.1
RXRG	NM_001256571.2	c.875+6A>G		splice_region_variant, intron_variant	Intron 8 of 8		NP_001243500.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RXRG	ENST00000359842.10	c.1244+6A>G		splice_region_variant, intron_variant	Intron 9 of 9	1	NM_006917.5	ENSP00000352900.5
RXRG	ENST00000619224.1	c.875+6A>G		splice_region_variant, intron_variant	Intron 10 of 10	1		ENSP00000482458.1
ENSG00000298458	ENST00000755607.1	n.513+14606T>C		intron_variant	Intron 3 of 3

Frequencies

GnomAD3 genomes AF: 0.823 AC: 125208 AN: 152052 Hom.: 51751 Cov.: 32

Gnomad AFR AF: 0.873

Gnomad AMI AF: 0.759

Gnomad AMR AF: 0.786

Gnomad ASJ AF: 0.724

Gnomad EAS AF: 0.927

Gnomad SAS AF: 0.906

Gnomad FIN AF: 0.881

Gnomad MID AF: 0.726

Gnomad NFE AF: 0.786

Gnomad OTH AF: 0.792

GnomAD2 exomes AF: 0.828 AC: 207667 AN: 250900 AF XY: 0.828

Gnomad AFR exome AF: 0.876

Gnomad AMR exome AF: 0.827

Gnomad ASJ exome AF: 0.727

Gnomad EAS exome AF: 0.924

Gnomad FIN exome AF: 0.875

Gnomad NFE exome AF: 0.786

Gnomad OTH exome AF: 0.811

GnomAD4 exome AF: 0.804 AC: 1171015 AN: 1455974 Hom.: 472510 Cov.: 30 AF XY: 0.807 AC XY: 584449 AN XY: 724628

African (AFR) AF: 0.879 AC: 29313 AN: 33344

American (AMR) AF: 0.825 AC: 36890 AN: 44698

Ashkenazi Jewish (ASJ) AF: 0.734 AC: 19138 AN: 26086

East Asian (EAS) AF: 0.939 AC: 37244 AN: 39668

South Asian (SAS) AF: 0.901 AC: 77650 AN: 86140

European-Finnish (FIN) AF: 0.867 AC: 46143 AN: 53228

Middle Eastern (MID) AF: 0.804 AC: 4603 AN: 5722

European-Non Finnish (NFE) AF: 0.787 AC: 871613 AN: 1106876

Other (OTH) AF: 0.804 AC: 48421 AN: 60212

GnomAD4 genome AF: 0.823 AC: 125311 AN: 152170 Hom.: 51796 Cov.: 32 AF XY: 0.829 AC XY: 61658 AN XY: 74390

African (AFR) AF: 0.873 AC: 36242 AN: 41502

American (AMR) AF: 0.785 AC: 12013 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.724 AC: 2513 AN: 3472

East Asian (EAS) AF: 0.927 AC: 4798 AN: 5176

South Asian (SAS) AF: 0.905 AC: 4357 AN: 4814

European-Finnish (FIN) AF: 0.881 AC: 9344 AN: 10604

Middle Eastern (MID) AF: 0.733 AC: 214 AN: 292

European-Non Finnish (NFE) AF: 0.786 AC: 53464 AN: 67996

Other (OTH) AF: 0.794 AC: 1675 AN: 2110

Alfa AF: 0.801 Hom.: 34070

Bravo AF: 0.818

Asia WGS AF: 0.919 AC: 3198 AN: 3478

EpiCase AF: 0.772

EpiControl AF: 0.777

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	2.6
DANN	Benign	0.76
PhyloP100		-0.75
Mutation Taster		=98/2	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00014
dbscSNV1_RF	Benign	0.0040
SpliceAI score (max)		0.020		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: rs283696; hg19: chr1-165376043;