Genetic Variant RXRB:c.*231T>A (chr6-33194451-A-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The NM_021976.5(RXRB):c.*231T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.117 in 506,762 control chromosomes in the GnomAD database, including 4,392 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as (no stars).

Frequency

Genomes: 𝑓 0.11 ( 1320 hom., cov: 32)

Exomes 𝑓: 0.12 ( 3072 hom. )

Consequence

RXRB
NM_021976.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.141

Publications

7 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 -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.28).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.224 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021976.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
RXRB	NM_021976.5	MANE Select	c.*231T>A	3_prime_UTR	Exon 10 of 10	NP_068811.1
RXRB	NM_001270401.2		c.*231T>A	3_prime_UTR	Exon 10 of 10	NP_001257330.1
RXRB	NM_001291989.2		c.*231T>A	3_prime_UTR	Exon 9 of 9	NP_001278918.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
RXRB	ENST00000374680.4	TSL:1 MANE Select	c.*231T>A	3_prime_UTR	Exon 10 of 10	ENSP00000363812.3
RXRB	ENST00000374685.8	TSL:1	c.*231T>A	3_prime_UTR	Exon 10 of 10	ENSP00000363817.4
RXRB	ENST00000865272.1		c.*231T>A	3_prime_UTR	Exon 10 of 10	ENSP00000535331.1

Frequencies

GnomAD3 genomes

AF:

0.107

AC:

16232

AN:

152194

Hom.:

1316

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0217

Gnomad AMI

AF:

0.0724

Gnomad AMR

AF:

0.230

Gnomad ASJ

AF:

0.0781

Gnomad EAS

AF:

0.0327

Gnomad SAS

AF:

0.0720

Gnomad FIN

AF:

0.210

Gnomad MID

AF:

0.0949

Gnomad NFE

AF:

0.125

Gnomad OTH

AF:

0.0958

GnomAD4 exome

AF:

0.122

AC:

43170

AN:

354450

Hom.:

3072

Cov.:

AF XY:

0.120

AC XY:

22067

AN XY:

183450

show subpopulations

African (AFR)

AF:

0.0203

AC:

209

AN:

10298

American (AMR)

AF:

0.280

AC:

3558

AN:

12696

Ashkenazi Jewish (ASJ)

AF:

0.0874

AC:

1017

AN:

11630

East Asian (EAS)

AF:

0.0669

AC:

1791

AN:

26786

South Asian (SAS)

AF:

0.0708

AC:

1700

AN:

24018

European-Finnish (FIN)

AF:

0.197

AC:

4984

AN:

25362

Middle Eastern (MID)

AF:

0.139

AC:

232

AN:

1670

European-Non Finnish (NFE)

AF:

0.124

AC:

27233

AN:

220170

Other (OTH)

AF:

0.112

AC:

2446

AN:

21820

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1733

3466

5199

6932

8665

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

178

356

534

712

890

<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:

0.107

AC:

16244

AN:

152312

Hom.:

1320

Cov.:

AF XY:

0.111

AC XY:

8286

AN XY:

74480

show subpopulations

African (AFR)

AF:

0.0217

AC:

901

AN:

41586

American (AMR)

AF:

0.230

AC:

3519

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.0781

AC:

271

AN:

3472

East Asian (EAS)

AF:

0.0333

AC:

173

AN:

5194

South Asian (SAS)

AF:

0.0739

AC:

357

AN:

4830

European-Finnish (FIN)

AF:

0.210

AC:

2228

AN:

10606

Middle Eastern (MID)

AF:

0.0986

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.125

AC:

8502

AN:

68006

Other (OTH)

AF:

0.0938

AC:

198

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

716

1432

2149

2865

3581

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

170

340

510

680

850

<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:

0.114

Hom.:

165

Bravo

AF:

0.108

Asia WGS

AF:

0.0480

AC:

168

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.28

CADD

Benign

9.6

(source)

DANN

Benign

0.77

PhyloP100

0.14

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over