chr6-33194833-G-GGGTGGA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBS1BS2

The NM_021976.5(RXRB):​c.1455-5_1455-4insTCCACC variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00201 in 1,612,780 control chromosomes in the GnomAD database, including 230 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0029 ( 24 hom., cov: 32)
Exomes 𝑓: 0.0019 ( 206 hom. )

Consequence

RXRB
NM_021976.5 splice_region, splice_polypyrimidine_tract, intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 1.10
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.

BP6
Variant 6-33194833-G-GGGTGGA is Benign according to our data. Variant chr6-33194833-G-GGGTGGA is described in ClinVar as [Benign]. Clinvar id is 779906.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00294 (448/152326) while in subpopulation EAS AF= 0.0519 (269/5184). AF 95% confidence interval is 0.0468. There are 24 homozygotes in gnomad4. There are 251 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High AC in GnomAd4 at 448 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
RXRBNM_021976.5 linkuse as main transcriptc.1455-5_1455-4insTCCACC splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant ENST00000374680.4 NP_068811.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
RXRBENST00000374680.4 linkuse as main transcriptc.1455-5_1455-4insTCCACC splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant 1 NM_021976.5 ENSP00000363812 P4P28702-1
RXRBENST00000374685.8 linkuse as main transcriptc.1467-5_1467-4insTCCACC splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant 1 ENSP00000363817 A1P28702-3
RXRBENST00000483281.5 linkuse as main transcriptc.*967-5_*967-4insTCCACC splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, NMD_transcript_variant 5 ENSP00000431369
RXRBENST00000483821.1 linkuse as main transcriptn.417-5_417-4insTCCACC splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant 2

Frequencies

GnomAD3 genomes
AF:
0.00297
AC:
452
AN:
152208
Hom.:
25
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000917
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00111
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.0523
Gnomad SAS
AF:
0.0232
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00526
GnomAD3 exomes
AF:
0.00521
AC:
1283
AN:
246186
Hom.:
39
AF XY:
0.00517
AC XY:
694
AN XY:
134206
show subpopulations
Gnomad AFR exome
AF:
0.000794
Gnomad AMR exome
AF:
0.000639
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0510
Gnomad SAS exome
AF:
0.00911
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000272
Gnomad OTH exome
AF:
0.00611
GnomAD4 exome
AF:
0.00192
AC:
2801
AN:
1460454
Hom.:
206
Cov.:
32
AF XY:
0.00199
AC XY:
1446
AN XY:
726516
show subpopulations
Gnomad4 AFR exome
AF:
0.000388
Gnomad4 AMR exome
AF:
0.000537
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0268
Gnomad4 SAS exome
AF:
0.00963
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000189
Gnomad4 OTH exome
AF:
0.0140
GnomAD4 genome
AF:
0.00294
AC:
448
AN:
152326
Hom.:
24
Cov.:
32
AF XY:
0.00337
AC XY:
251
AN XY:
74490
show subpopulations
Gnomad4 AFR
AF:
0.000914
Gnomad4 AMR
AF:
0.00111
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.0519
Gnomad4 SAS
AF:
0.0230
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00521
Alfa
AF:
0.00158
Hom.:
3
Asia WGS
AF:
0.0500
AC:
175
AN:
3478
EpiCase
AF:
0.0000545
EpiControl
AF:
0.0000593

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

RXRB-related disorder Benign:1
Benign, no assertion criteria providedclinical testingPreventionGenetics, part of Exact SciencesOct 21, 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 testingLabcorp Genetics (formerly Invitae), LabcorpDec 31, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

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: rs143154990; hg19: chr6-33162610; API