1-165428917-C-T

Variant names:

• chr1-165428917-C-T
• rs1278232099
• NM_006917.5:c.99G>A

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_006917.5(RXRG):​c.99G>A​(p.Leu33Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: RXRG NM_006917.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.153
• Publications: 0 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]

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.28).
• BP7: Synonymous conserved (PhyloP=-0.153 with no splicing effect.

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.99G>A	p.Leu33Leu	synonymous	Exon 2 of 10	NP_008848.1	P48443
	RXRG	NM_001256570.2		c.-329G>A		5_prime_UTR	Exon 2 of 11	NP_001243499.1	A0A087WZ88

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RXRG	ENST00000359842.10	TSL:1 MANE Select	c.99G>A	p.Leu33Leu	synonymous	Exon 2 of 10	ENSP00000352900.5	P48443
	RXRG	ENST00000619224.1	TSL:1	c.-329G>A		5_prime_UTR	Exon 2 of 11	ENSP00000482458.1	A0A087WZ88
	RXRG	ENST00000885409.1		c.99G>A	p.Leu33Leu	synonymous	Exon 2 of 10	ENSP00000555468.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.28
CADD	Benign	7.8
DANN	Benign	0.80
PhyloP100		-0.15
Mutation Taster		=100/0	polymorphism

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: rs1278232099; hg19: chr1-165398154;