dbSNP rs1394273977: RXRG:c.-258G>C (chr1-165428846-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001256570.2(RXRG):c.-258G>C variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,860 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

RXRG
NM_001256570.2 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.781

Publications

0 publications found

Variant links:

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]

RXRG links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.13111678).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001256570.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RXRG	NM_006917.5	MANE Select	c.170G>C	p.Ser57Thr	missense	Exon 2 of 10	NP_008848.1	P48443
RXRG	NM_001256570.2		c.-258G>C		5_prime_UTR_premature_start_codon_gain	Exon 2 of 11	NP_001243499.1	A0A087WZ88
RXRG	NM_001256570.2		c.-258G>C		5_prime_UTR	Exon 2 of 11	NP_001243499.1	A0A087WZ88

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RXRG	ENST00000619224.1	TSL:1	c.-258G>C		5_prime_UTR_premature_start_codon_gain	Exon 2 of 11	ENSP00000482458.1	A0A087WZ88
RXRG	ENST00000359842.10	TSL:1 MANE Select	c.170G>C	p.Ser57Thr	missense	Exon 2 of 10	ENSP00000352900.5	P48443
RXRG	ENST00000619224.1	TSL:1	c.-258G>C		5_prime_UTR	Exon 2 of 11	ENSP00000482458.1	A0A087WZ88

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461860

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727232

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.00

AC:

AN:

86254

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1111990

Other (OTH)

AF:

0.00

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.062

BayesDel_addAF

Benign

-0.063

BayesDel_noAF

Benign

-0.33

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Uncertain

0.42

Eigen

Benign

-0.31

Eigen_PC

Benign

-0.15

FATHMM_MKL

Benign

0.65

LIST_S2

Benign

0.63

M_CAP

Benign

0.023

MetaRNN

Benign

0.13

MetaSVM

Benign

-0.69

MutationAssessor

Benign

0.78

PhyloP100

0.78

PrimateAI

Uncertain

0.62

PROVEAN

Benign

-0.68

REVEL

Benign

0.18

Sift

Benign

0.26

Sift4G

Benign

0.42

Polyphen

0.0030

Vest4

0.16

MutPred

0.16

Loss of glycosylation at S57 (P = 0.1042)

MVP

0.51

MPC

0.056

ClinPred

0.17

GERP RS

3.8

Varity_R

0.076

gMVP

0.50

Mutation Taster

=92/8

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over