Variant 6-33197947-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_021976.5(RXRB):c.641-6C>G 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 0.00137 in 1,612,392 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.0023 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0013 ( 16 hom. )

Consequence

RXRB
NM_021976.5 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.0003243

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.401

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]

RXRB links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 6-33197947-G-C is Benign according to our data. Variant chr6-33197947-G-C is described in ClinVar as [Benign]. Clinvar id is 3034436.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High AC in GnomAd4 at 349 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RXRB	NM_021976.5 linkuse as main transcript	c.641-6C>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000374680.4	NP_068811.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris	UniProt
RXRB	ENST00000374680.4 linkuse as main transcript	c.641-6C>G	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	1	NM_021976.5	ENSP00000363812	P4	P28702-1
RXRB	ENST00000374685.8 linkuse as main transcript	c.641-6C>G	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	1		ENSP00000363817	A1	P28702-3
RXRB	ENST00000483281.5 linkuse as main transcript	c.*153-6C>G	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, NMD_transcript_variant	5		ENSP00000431369
RXRB	ENST00000481441.1 linkuse as main transcript	n.329-6C>G	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant	2

Frequencies

GnomAD3 genomes

AF:

0.00229

AC:

349

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00589

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00137

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000963

Gnomad SAS

AF:

0.0136

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00261

AC:

638

AN:

244614

Hom.:

AF XY:

0.00320

AC XY:

427

AN XY:

133234

show subpopulations

Gnomad AFR exome

AF:

0.00704

Gnomad AMR exome

AF:

0.000380

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000439

Gnomad SAS exome

AF:

0.0164

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000100

Gnomad OTH exome

AF:

0.000829

GnomAD4 exome

AF:

0.00127

AC:

1855

AN:

1460074

Hom.:

Cov.:

AF XY:

0.00163

AC XY:

1184

AN XY:

726300

show subpopulations

Gnomad4 AFR exome

AF:

0.00678

Gnomad4 AMR exome

AF:

0.000381

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.0143

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000254

Gnomad4 OTH exome

AF:

0.00156

GnomAD4 genome

AF:

0.00229

AC:

349

AN:

152318

Hom.:

Cov.:

AF XY:

0.00251

AC XY:

187

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.00590

Gnomad4 AMR

AF:

0.00137

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000965

Gnomad4 SAS

AF:

0.0135

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.000804

Hom.:

Bravo

AF:

0.00224

Asia WGS

AF:

0.0120

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

RXRB-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 18, 2019

This variant is classified as 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

-0.85

CADD

Benign

0.39

DANN

Benign

0.67

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00032

dbscSNV1_RF

Benign

0.038

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over