Menu
GeneBe

6-33195620-G-A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_021976.5(RXRB):c.1206C>T(p.His402=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000153 in 1,613,088 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.00018 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00015 ( 0 hom. )

Consequence

RXRB
NM_021976.5 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.24
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 Benign. Variant got -11 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=-0.59).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 6-33195620-G-A is Benign according to our data. Variant chr6-33195620-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3049286.Status of the report is criteria_provided_single_submitter, 1 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=-1.24 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 29 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RXRBNM_021976.5 linkuse as main transcriptc.1206C>T p.His402= synonymous_variant 7/10 ENST00000374680.4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RXRBENST00000374680.4 linkuse as main transcriptc.1206C>T p.His402= synonymous_variant 7/101 NM_021976.5 P4P28702-1
RXRBENST00000374685.8 linkuse as main transcriptc.1206C>T p.His402= synonymous_variant 7/101 A1P28702-3
RXRBENST00000483281.5 linkuse as main transcriptc.*718C>T 3_prime_UTR_variant, NMD_transcript_variant 6/95

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000191
AC:
29
AN:
152218
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00366
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000118
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000308
AC:
76
AN:
246528
Hom.:
0
AF XY:
0.000320
AC XY:
43
AN XY:
134382
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00372
Gnomad SAS exome
AF:
0.000132
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000362
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000150
AC:
219
AN:
1460752
Hom.:
0
Cov.:
31
AF XY:
0.000149
AC XY:
108
AN XY:
726688
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00327
Gnomad4 SAS exome
AF:
0.000209
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000423
Gnomad4 OTH exome
AF:
0.000381
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000184
AC:
28
AN:
152336
Hom.:
0
Cov.:
32
AF XY:
0.000228
AC XY:
17
AN XY:
74488
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00347
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000118
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000818
Hom.:
0
Bravo
AF:
0.000268
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

ClinVar

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

Submissions by phenotype

RXRB-related disorder Benign:1
Likely benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesJul 10, 2019This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.59
Cadd
Benign
0.77
Dann
Benign
0.87
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

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: rs184921826; hg19: chr6-33163397; COSMIC: COSV59499300; COSMIC: COSV59499300; API