dbSNP rs6531: RXRB:p.Phe384Phe (chr6-33195674-G-A) – ACMG Classification: Benign (-15 pts)

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_021976.5(RXRB):c.1152C>T(p.Phe384Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.74 in 1,612,344 control chromosomes in the GnomAD database, including 444,715 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.77 ( 45628 hom., cov: 32)

Exomes 𝑓: 0.74 ( 399087 hom. )

Consequence

RXRB
NM_021976.5 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 2.99

Publications

52 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.53).

BP6

Variant 6-33195674-G-A is Benign according to our data. Variant chr6-33195674-G-A is described in ClinVar as Benign. ClinVar VariationId is 1254260.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=2.99 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.946 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RXRB	NM_021976.5 link	c.1152C>T	p.Phe384Phe	synonymous_variant	Exon 7 of 10	ENST00000374680.4	NP_068811.1	P28702-1Q5STP9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RXRB	ENST00000374680.4 link	c.1152C>T	p.Phe384Phe	synonymous_variant	Exon 7 of 10	1	NM_021976.5	ENSP00000363812.3		P28702-1

Frequencies

GnomAD3 genomes

AF:

0.771

AC:

117207

AN:

151966

Hom.:

45589

Cov.:

show subpopulations

Gnomad AFR

AF:

0.835

Gnomad AMI

AF:

0.605

Gnomad AMR

AF:

0.784

Gnomad ASJ

AF:

0.800

Gnomad EAS

AF:

0.968

Gnomad SAS

AF:

0.872

Gnomad FIN

AF:

0.708

Gnomad MID

AF:

0.816

Gnomad NFE

AF:

0.717

Gnomad OTH

AF:

0.791

GnomAD2 exomes

AF:

0.775

AC:

190210

AN:

245492

AF XY:

0.776

show subpopulations

Gnomad AFR exome

AF:

0.840

Gnomad AMR exome

AF:

0.794

Gnomad ASJ exome

AF:

0.810

Gnomad EAS exome

AF:

0.974

Gnomad FIN exome

AF:

0.699

Gnomad NFE exome

AF:

0.715

Gnomad OTH exome

AF:

0.774

GnomAD4 exome

AF:

0.737

AC:

1075707

AN:

1460260

Hom.:

399087

Cov.:

AF XY:

0.740

AC XY:

537907

AN XY:

726424

show subpopulations

African (AFR)

AF:

0.848

AC:

28383

AN:

33478

American (AMR)

AF:

0.797

AC:

35591

AN:

44676

Ashkenazi Jewish (ASJ)

AF:

0.810

AC:

21159

AN:

26132

East Asian (EAS)

AF:

0.981

AC:

38955

AN:

39700

South Asian (SAS)

AF:

0.857

AC:

73900

AN:

86246

European-Finnish (FIN)

AF:

0.702

AC:

36570

AN:

52130

Middle Eastern (MID)

AF:

0.829

AC:

4780

AN:

5768

European-Non Finnish (NFE)

AF:

0.711

AC:

790798

AN:

1111762

Other (OTH)

AF:

0.755

AC:

45571

AN:

60368

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

16155

32310

48466

64621

80776

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19924

39848

59772

79696

99620

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.771

AC:

117302

AN:

152084

Hom.:

45628

Cov.:

AF XY:

0.772

AC XY:

57400

AN XY:

74322

show subpopulations

African (AFR)

AF:

0.835

AC:

34632

AN:

41490

American (AMR)

AF:

0.784

AC:

11977

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.800

AC:

2773

AN:

3468

East Asian (EAS)

AF:

0.968

AC:

5010

AN:

5176

South Asian (SAS)

AF:

0.871

AC:

4198

AN:

4818

European-Finnish (FIN)

AF:

0.708

AC:

7480

AN:

10568

Middle Eastern (MID)

AF:

0.823

AC:

242

AN:

294

European-Non Finnish (NFE)

AF:

0.717

AC:

48765

AN:

67968

Other (OTH)

AF:

0.794

AC:

1673

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1343

2687

4030

5374

6717

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

862

1724

2586

3448

4310

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.744

Hom.:

93182

Bravo

AF:

0.781

Asia WGS

AF:

0.879

AC:

3057

AN:

3478

EpiCase

AF:

0.732

EpiControl

AF:

0.739

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

RXRB-related disorder

Benign:1

Oct 16, 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

Sep 27, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

(source)

DANN

Benign

0.87

PhyloP100

3.0

Mutation Taster

=99/1

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over