Genetic Variant RXRB:c.1455-10_1455-5dupTCCACC (chr6-33194833-G-GGGTGGA) – ACMG Classification: Benign (-10 pts)

Variant summary

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

The NM_021976.5(RXRB):c.1455-10_1455-5dupTCCACC variant causes a splice region, 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, 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]

RXRB links:

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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 rank	MANE	Protein	UniProt
RXRB	NM_021976.5 link	c.1455-10_1455-5dupTCCACC		splice_region_variant, intron_variant	Intron 9 of 9	ENST00000374680.4	NP_068811.1	P28702-1Q5STP9

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
RXRB	ENST00000374680.4 link	c.1455-5_1455-4insTCCACC	splice_region_variant, intron_variant	Intron 9 of 9	1	NM_021976.5	ENSP00000363812.3	P28702-1
RXRB	ENST00000374685.8 link	c.1467-5_1467-4insTCCACC	splice_region_variant, intron_variant	Intron 9 of 9	1		ENSP00000363817.4	P28702-3
RXRB	ENST00000483281.5 link	n.967-5_967-4insTCCACC	splice_region_variant, intron_variant	Intron 8 of 8	5		ENSP00000431369.1	E9PK75
RXRB	ENST00000483821.1 link	n.417-5_417-4insTCCACC	splice_region_variant, intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes

AF:

0.00297

AC:

452

AN:

152208

Hom.:

Cov.:

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.:

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.:

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.:

Cov.:

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.:

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

Oct 21, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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). -

not provided

Benign:1

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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.

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