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GeneBe

rs6531

chr6-33195674-G-Achr6-33195674-G-Cchr6-33195674-G-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_021976.5(RXRB):c.1152C>T(p.Phe384=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.74 in 1,612,344 control chromosomes in the GnomAD database, including 444,715 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.77 ( 45628 hom., cov: 32)
Exomes 𝑓: 0.74 ( 399087 hom. )

Consequence

RXRB
NM_021976.5 synonymous

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.99
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 -21 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.53).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 6-33195674-G-A is Benign according to our data. Variant chr6-33195674-G-A is described in ClinVar as [Benign]. Clinvar id is 1254260.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=2.99 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.946 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RXRBNM_021976.5 linkuse as main transcriptc.1152C>T p.Phe384= synonymous_variant 7/10 ENST00000374680.4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RXRBENST00000374680.4 linkuse as main transcriptc.1152C>T p.Phe384= synonymous_variant 7/101 NM_021976.5 P4P28702-1
RXRBENST00000374685.8 linkuse as main transcriptc.1152C>T p.Phe384= synonymous_variant 7/101 A1P28702-3
RXRBENST00000483281.5 linkuse as main transcriptc.*664C>T 3_prime_UTR_variant, NMD_transcript_variant 6/95

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.771
AC:
117207
AN:
151966
Hom.:
45589
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.835
Gnomad AMI
AF:
0.605
Gnomad AMR
AF:
0.784
Gnomad ASJ
AF:
0.800
Gnomad EAS
AF:
0.968
Gnomad SAS
AF:
0.872
Gnomad FIN
AF:
0.708
Gnomad MID
AF:
0.816
Gnomad NFE
AF:
0.717
Gnomad OTH
AF:
0.791
GnomAD3 exomes
AF:
0.775
AC:
190210
AN:
245492
Hom.:
74523
AF XY:
0.776
AC XY:
103808
AN XY:
133834
show subpopulations
Gnomad AFR exome
AF:
0.840
Gnomad AMR exome
AF:
0.794
Gnomad ASJ exome
AF:
0.810
Gnomad EAS exome
AF:
0.974
Gnomad SAS exome
AF:
0.859
Gnomad FIN exome
AF:
0.699
Gnomad NFE exome
AF:
0.715
Gnomad OTH exome
AF:
0.774
GnomAD4 exome
AF:
0.737
AC:
1075707
AN:
1460260
Hom.:
399087
Cov.:
56
AF XY:
0.740
AC XY:
537907
AN XY:
726424
show subpopulations
Gnomad4 AFR exome
AF:
0.848
Gnomad4 AMR exome
AF:
0.797
Gnomad4 ASJ exome
AF:
0.810
Gnomad4 EAS exome
AF:
0.981
Gnomad4 SAS exome
AF:
0.857
Gnomad4 FIN exome
AF:
0.702
Gnomad4 NFE exome
AF:
0.711
Gnomad4 OTH exome
AF:
0.755
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.771
AC:
117302
AN:
152084
Hom.:
45628
Cov.:
32
AF XY:
0.772
AC XY:
57400
AN XY:
74322
show subpopulations
Gnomad4 AFR
AF:
0.835
Gnomad4 AMR
AF:
0.784
Gnomad4 ASJ
AF:
0.800
Gnomad4 EAS
AF:
0.968
Gnomad4 SAS
AF:
0.871
Gnomad4 FIN
AF:
0.708
Gnomad4 NFE
AF:
0.717
Gnomad4 OTH
AF:
0.794
Alfa
AF:
0.737
Hom.:
59707
Bravo
AF:
0.781
Asia WGS
AF:
0.879
AC:
3057
AN:
3478
EpiCase
AF:
0.732
EpiControl
AF:
0.739

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

RXRB-related disorder Benign:1
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesOct 16, 2019This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
not provided Benign:1
Benign, criteria provided, single submitterclinical testingGeneDxSep 27, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.53
Cadd
Benign
11
Dann
Benign
0.87

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.060
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: rs6531; hg19: chr6-33163451; COSMIC: COSV59500334; COSMIC: COSV59500334; API