chr6-33199179-C-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_021976.5(RXRB):​c.473G>A​(p.Ser158Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000027 in 1,297,738 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 29)
Exomes 𝑓: 0.000028 ( 0 hom. )

Consequence

RXRB
NM_021976.5 missense

Scores

1
7
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.37
Variant links:
Genes affected
RXRB (HGNC:10478): (retinoid X receptor beta) This gene encodes a member of the retinoid X receptor (RXR) family of nuclear receptors which are involved in mediating the effects of retinoic acid (RA). The encoded protein forms homodimers with the retinoic acid, thyroid hormone, and vitamin D receptors, increasing both DNA binding and transcriptional function on their respective response elements. This gene lies within the major histocompatibility complex (MHC) class II region on chromosome 6. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Jul 2012]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.23888227).
BS2
High AC in GnomAdExome4 at 32 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
RXRBNM_021976.5 linkuse as main transcriptc.473G>A p.Ser158Asn missense_variant 2/10 ENST00000374680.4 NP_068811.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
RXRBENST00000374680.4 linkuse as main transcriptc.473G>A p.Ser158Asn missense_variant 2/101 NM_021976.5 ENSP00000363812 P4P28702-1
RXRBENST00000374685.8 linkuse as main transcriptc.473G>A p.Ser158Asn missense_variant 2/101 ENSP00000363817 A1P28702-3
RXRBENST00000483281.5 linkuse as main transcriptc.236-715G>A intron_variant, NMD_transcript_variant 5 ENSP00000431369

Frequencies

GnomAD3 genomes
AF:
0.0000198
AC:
3
AN:
151686
Hom.:
0
Cov.:
29
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000441
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.0000279
AC:
32
AN:
1146052
Hom.:
0
Cov.:
30
AF XY:
0.0000183
AC XY:
10
AN XY:
546622
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000657
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000316
Gnomad4 OTH exome
AF:
0.0000218
GnomAD4 genome
AF:
0.0000198
AC:
3
AN:
151686
Hom.:
0
Cov.:
29
AF XY:
0.0000270
AC XY:
2
AN XY:
74054
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000441
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000712
Hom.:
0
Bravo
AF:
0.0000189
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000120
AC:
1
ExAC
AF:
0.0000272
AC:
3

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsOct 04, 2022The c.473G>A (p.S158N) alteration is located in exon 2 (coding exon 2) of the RXRB gene. This alteration results from a G to A substitution at nucleotide position 473, causing the serine (S) at amino acid position 158 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.15
BayesDel_addAF
Uncertain
0.039
T
BayesDel_noAF
Benign
-0.18
CADD
Uncertain
24
DANN
Uncertain
0.99
DEOGEN2
Benign
0.40
.;T
Eigen
Uncertain
0.40
Eigen_PC
Uncertain
0.41
FATHMM_MKL
Uncertain
0.88
D
M_CAP
Benign
0.072
D
MetaRNN
Benign
0.24
T;T
MetaSVM
Uncertain
0.069
D
MutationAssessor
Benign
1.4
L;L
MutationTaster
Benign
1.0
D;D;D;D
PrimateAI
Pathogenic
0.85
D
PROVEAN
Benign
-1.1
N;N
REVEL
Uncertain
0.34
Sift
Benign
0.035
D;D
Sift4G
Benign
0.28
T;T
Polyphen
0.97
.;D
Vest4
0.18
MVP
0.84
MPC
0.42
ClinPred
0.23
T
GERP RS
5.0
Varity_R
0.14
gMVP
0.12

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs369876854; hg19: chr6-33166956; API