Genetic Variant RXRB:c.*377A>T (chr6-33194305-T-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_021976.5(RXRB):c.*377A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.313 in 178,948 control chromosomes in the GnomAD database, including 9,084 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.32 ( 7751 hom., cov: 32)

Exomes 𝑓: 0.30 ( 1333 hom. )

Consequence

RXRB
NM_021976.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.399

Publications

34 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.54).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.369 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RXRB	NM_021976.5 link	c.*377A>T		3_prime_UTR_variant	Exon 10 of 10	ENST00000374680.4	NP_068811.1	P28702-1Q5STP9

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
RXRB	ENST00000374680.4 link	c.*377A>T	3_prime_UTR_variant	Exon 10 of 10	1	NM_021976.5	ENSP00000363812.3	P28702-1
RXRB	ENST00000374685.8 link	c.*377A>T	3_prime_UTR_variant	Exon 10 of 10	1		ENSP00000363817.4	P28702-3
RXRB	ENST00000483281.5 link	n.*1491A>T	non_coding_transcript_exon_variant	Exon 9 of 9	5		ENSP00000431369.1	E9PK75
RXRB	ENST00000483281.5 link	n.*1491A>T	3_prime_UTR_variant	Exon 9 of 9	5		ENSP00000431369.1	E9PK75

Frequencies

GnomAD3 genomes

AF:

0.316

AC:

47884

AN:

151692

Hom.:

7748

Cov.:

show subpopulations

Gnomad AFR

AF:

0.361

Gnomad AMI

AF:

0.411

Gnomad AMR

AF:

0.269

Gnomad ASJ

AF:

0.378

Gnomad EAS

AF:

0.228

Gnomad SAS

AF:

0.384

Gnomad FIN

AF:

0.205

Gnomad MID

AF:

0.366

Gnomad NFE

AF:

0.313

Gnomad OTH

AF:

0.323

GnomAD4 exome

AF:

0.300

AC:

8141

AN:

27136

Hom.:

1333

Cov.:

AF XY:

0.300

AC XY:

4170

AN XY:

13918

show subpopulations

African (AFR)

AF:

0.361

AC:

320

AN:

886

American (AMR)

AF:

0.239

AC:

276

AN:

1154

Ashkenazi Jewish (ASJ)

AF:

0.383

AC:

390

AN:

1018

East Asian (EAS)

AF:

0.217

AC:

399

AN:

1836

South Asian (SAS)

AF:

0.374

AC:

459

AN:

1226

European-Finnish (FIN)

AF:

0.221

AC:

210

AN:

950

Middle Eastern (MID)

AF:

0.338

AC:

AN:

142

European-Non Finnish (NFE)

AF:

0.302

AC:

5489

AN:

18148

Other (OTH)

AF:

0.310

AC:

550

AN:

1776

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

288

577

865

1154

1442

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

138

184

230

<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:

0.316

AC:

47902

AN:

151812

Hom.:

7751

Cov.:

AF XY:

0.310

AC XY:

22995

AN XY:

74172

show subpopulations

African (AFR)

AF:

0.361

AC:

14916

AN:

41370

American (AMR)

AF:

0.269

AC:

4109

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.378

AC:

1311

AN:

3468

East Asian (EAS)

AF:

0.227

AC:

1164

AN:

5132

South Asian (SAS)

AF:

0.384

AC:

1837

AN:

4786

European-Finnish (FIN)

AF:

0.205

AC:

2160

AN:

10554

Middle Eastern (MID)

AF:

0.367

AC:

108

AN:

294

European-Non Finnish (NFE)

AF:

0.313

AC:

21247

AN:

67916

Other (OTH)

AF:

0.321

AC:

678

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1698

3395

5093

6790

8488

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

478

956

1434

1912

2390

<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:

0.319

Hom.:

4543

Bravo

AF:

0.318

Asia WGS

AF:

0.329

AC:

1146

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

(source)

DANN

Benign

0.87

PhyloP100

0.40

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over