Genetic Variant RXRB:c.640+51T>C (chr6-33198257-A-G) – 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.640+51T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.26 in 1,610,972 control chromosomes in the GnomAD database, including 59,525 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 0.29 ( 7039 hom., cov: 32)

Exomes 𝑓: 0.26 ( 52486 hom. )

Consequence

RXRB
NM_021976.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.102

Publications

42 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=-0.9).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.62 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	UniProt
RXRB	NM_021976.5	MANE Select	c.640+51T>C	intron	N/A	NP_068811.1	Q5STP9
RXRB	NM_001270401.2		c.640+51T>C	intron	N/A	NP_001257330.1	A0A0S2Z570
RXRB	NM_001291989.2		c.70+51T>C	intron	N/A	NP_001278918.1	A0A0G2JKR7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
RXRB	ENST00000374680.4	TSL:1 MANE Select	c.640+51T>C	intron	N/A	ENSP00000363812.3	P28702-1
RXRB	ENST00000374685.8	TSL:1	c.640+51T>C	intron	N/A	ENSP00000363817.4	P28702-3
RXRB	ENST00000865272.1		c.640+51T>C	intron	N/A	ENSP00000535331.1

Frequencies

GnomAD3 genomes

AF:

0.288

AC:

43752

AN:

151954

Hom.:

7012

Cov.:

show subpopulations

Gnomad AFR

AF:

0.365

Gnomad AMI

AF:

0.137

Gnomad AMR

AF:

0.231

Gnomad ASJ

AF:

0.168

Gnomad EAS

AF:

0.637

Gnomad SAS

AF:

0.303

Gnomad FIN

AF:

0.271

Gnomad MID

AF:

0.241

Gnomad NFE

AF:

0.237

Gnomad OTH

AF:

0.297

GnomAD2 exomes

AF:

0.275

AC:

67006

AN:

243888

AF XY:

0.274

show subpopulations

Gnomad AFR exome

AF:

0.365

Gnomad AMR exome

AF:

0.191

Gnomad ASJ exome

AF:

0.180

Gnomad EAS exome

AF:

0.639

Gnomad FIN exome

AF:

0.262

Gnomad NFE exome

AF:

0.233

Gnomad OTH exome

AF:

0.262

GnomAD4 exome

AF:

0.257

AC:

374562

AN:

1458900

Hom.:

52486

Cov.:

AF XY:

0.257

AC XY:

186444

AN XY:

725866

show subpopulations

African (AFR)

AF:

0.354

AC:

11824

AN:

33442

American (AMR)

AF:

0.197

AC:

8813

AN:

44706

Ashkenazi Jewish (ASJ)

AF:

0.184

AC:

4808

AN:

26122

East Asian (EAS)

AF:

0.647

AC:

25663

AN:

39694

South Asian (SAS)

AF:

0.298

AC:

25706

AN:

86220

European-Finnish (FIN)

AF:

0.260

AC:

13605

AN:

52264

Middle Eastern (MID)

AF:

0.252

AC:

1441

AN:

5714

European-Non Finnish (NFE)

AF:

0.240

AC:

266552

AN:

1110426

Other (OTH)

AF:

0.268

AC:

16150

AN:

60312

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

15431

30861

46292

61722

77153

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9376

18752

28128

37504

46880

<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:

0.288

AC:

43826

AN:

152072

Hom.:

7039

Cov.:

AF XY:

0.290

AC XY:

21548

AN XY:

74338

show subpopulations

African (AFR)

AF:

0.365

AC:

15155

AN:

41470

American (AMR)

AF:

0.231

AC:

3525

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.168

AC:

584

AN:

3470

East Asian (EAS)

AF:

0.638

AC:

3293

AN:

5162

South Asian (SAS)

AF:

0.302

AC:

1455

AN:

4822

European-Finnish (FIN)

AF:

0.271

AC:

2866

AN:

10564

Middle Eastern (MID)

AF:

0.241

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.237

AC:

16108

AN:

67986

Other (OTH)

AF:

0.305

AC:

644

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1538

3076

4614

6152

7690

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

442

884

1326

1768

2210

<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:

0.255

Hom.:

17189

Bravo

AF:

0.293

Asia WGS

AF:

0.390

AC:

1353

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

5.2

(source)

DANN

Benign

0.72

PhyloP100

0.10

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