chr6-33196472-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_021976.5(RXRB):​c.955G>A​(p.Val319Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000146 in 1,613,080 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00014 ( 0 hom. )

Consequence

RXRB
NM_021976.5 missense

Scores

2
16

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.537
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.023199797).
BP6
Variant 6-33196472-C-T is Benign according to our data. Variant chr6-33196472-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2522153.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High AC in GnomAd4 at 30 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
RXRBNM_021976.5 linkuse as main transcriptc.955G>A p.Val319Ile missense_variant 5/10 ENST00000374680.4 NP_068811.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
RXRBENST00000374680.4 linkuse as main transcriptc.955G>A p.Val319Ile missense_variant 5/101 NM_021976.5 ENSP00000363812 P4P28702-1
RXRBENST00000374685.8 linkuse as main transcriptc.955G>A p.Val319Ile missense_variant 5/101 ENSP00000363817 A1P28702-3
RXRBENST00000481441.1 linkuse as main transcriptn.643G>A non_coding_transcript_exon_variant 3/32
RXRBENST00000483281.5 linkuse as main transcriptc.*467G>A 3_prime_UTR_variant, NMD_transcript_variant 4/95 ENSP00000431369

Frequencies

GnomAD3 genomes
AF:
0.000197
AC:
30
AN:
152220
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000965
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00105
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.0000941
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000118
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000239
AC:
59
AN:
246464
Hom.:
0
AF XY:
0.000231
AC XY:
31
AN XY:
134376
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000551
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000547
Gnomad SAS exome
AF:
0.000296
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000262
Gnomad OTH exome
AF:
0.000165
GnomAD4 exome
AF:
0.000141
AC:
206
AN:
1460742
Hom.:
0
Cov.:
32
AF XY:
0.000144
AC XY:
105
AN XY:
726684
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000604
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.000325
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000101
Gnomad4 OTH exome
AF:
0.000331
GnomAD4 genome
AF:
0.000197
AC:
30
AN:
152338
Hom.:
0
Cov.:
32
AF XY:
0.000242
AC XY:
18
AN XY:
74484
show subpopulations
Gnomad4 AFR
AF:
0.0000962
Gnomad4 AMR
AF:
0.00105
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.0000941
Gnomad4 NFE
AF:
0.000118
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000186
Hom.:
0
Bravo
AF:
0.000162
ExAC
AF:
0.000213
AC:
25
Asia WGS
AF:
0.000289
AC:
1
AN:
3478
EpiCase
AF:
0.000218
EpiControl
AF:
0.000415

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Likely benign, criteria provided, single submitterclinical testingAmbry GeneticsMar 21, 2023This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.072
BayesDel_addAF
Benign
-0.42
T
BayesDel_noAF
Benign
-0.49
CADD
Benign
18
DANN
Uncertain
0.99
DEOGEN2
Benign
0.32
.;T
Eigen
Benign
-0.33
Eigen_PC
Benign
-0.15
FATHMM_MKL
Uncertain
0.96
D
M_CAP
Benign
0.014
T
MetaRNN
Benign
0.023
T;T
MetaSVM
Benign
-0.65
T
MutationAssessor
Benign
0.28
N;N
MutationTaster
Benign
0.74
D;N;N;N
PrimateAI
Benign
0.36
T
PROVEAN
Benign
-0.34
N;N
REVEL
Benign
0.11
Sift
Benign
0.38
T;T
Sift4G
Benign
0.55
T;T
Polyphen
0.059
.;B
Vest4
0.087
MVP
0.38
MPC
0.83
ClinPred
0.013
T
GERP RS
4.0
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.027
gMVP
0.062

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

LitVar

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

Other links and lift over

dbSNP: rs201059237; hg19: chr6-33164249; API