Variant 6-33198324-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6BS1BS2

The NM_021976.5(RXRB):c.624C>T(p.Cys208=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00216 in 1,613,012 control chromosomes in the GnomAD database, including 81 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.0016 ( 5 hom., cov: 32)

Exomes 𝑓: 0.0022 ( 76 hom. )

Consequence

RXRB
NM_021976.5 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.82

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.

BP6

Variant 6-33198324-G-A is Benign according to our data. Variant chr6-33198324-G-A is described in ClinVar as [Benign]. Clinvar id is 3042895.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00156 (237/152292) while in subpopulation SAS AF= 0.0333 (161/4828). AF 95% confidence interval is 0.0291. There are 5 homozygotes in gnomad4. There are 155 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 237 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RXRB	NM_021976.5 linkuse as main transcript	c.624C>T	p.Cys208=	synonymous_variant	3/10	ENST00000374680.4	NP_068811.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RXRB	ENST00000374680.4 linkuse as main transcript	c.624C>T	p.Cys208=	synonymous_variant	3/10	1	NM_021976.5	ENSP00000363812	P4	P28702-1
RXRB	ENST00000374685.8 linkuse as main transcript	c.624C>T	p.Cys208=	synonymous_variant	3/10	1		ENSP00000363817	A1	P28702-3
RXRB	ENST00000481441.1 linkuse as main transcript	n.312C>T		non_coding_transcript_exon_variant	1/3	2
RXRB	ENST00000483281.5 linkuse as main transcript	c.*136C>T		3_prime_UTR_variant, NMD_transcript_variant	2/9	5		ENSP00000431369

Frequencies

GnomAD3 genomes

AF:

0.00154

AC:

235

AN:

152174

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000869

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00366

Gnomad SAS

AF:

0.0329

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000191

Gnomad OTH

AF:

0.000958

GnomAD3 exomes

AF:

0.00438

AC:

1077

AN:

245712

Hom.:

AF XY:

0.00589

AC XY:

789

AN XY:

134042

show subpopulations

Gnomad AFR exome

AF:

0.000995

Gnomad AMR exome

AF:

0.0000580

Gnomad ASJ exome

AF:

0.00181

Gnomad EAS exome

AF:

0.00241

Gnomad SAS exome

AF:

0.0318

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.000173

Gnomad OTH exome

AF:

0.00181

GnomAD4 exome

AF:

0.00223

AC:

3254

AN:

1460720

Hom.:

Cov.:

AF XY:

0.00318

AC XY:

2312

AN XY:

726682

show subpopulations

Gnomad4 AFR exome

AF:

0.000657

Gnomad4 AMR exome

AF:

0.0000671

Gnomad4 ASJ exome

AF:

0.00119

Gnomad4 EAS exome

AF:

0.00154

Gnomad4 SAS exome

AF:

0.0325

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000114

Gnomad4 OTH exome

AF:

0.00325

GnomAD4 genome

AF:

0.00156

AC:

237

AN:

152292

Hom.:

Cov.:

AF XY:

0.00208

AC XY:

155

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.000866

Gnomad4 AMR

AF:

0.0000653

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.00367

Gnomad4 SAS

AF:

0.0333

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000191

Gnomad4 OTH

AF:

0.000948

Alfa

AF:

0.000311

Hom.:

Bravo

AF:

0.000631

Asia WGS

AF:

0.0200

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.000415

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 27, 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

-0.52

CADD

Benign

DANN

Benign

0.80

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.21

Details are displayed if max score is > 0.2

DS_DL_spliceai

0.21

Position offset: -16

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