Genetic Variant RXRB:c.1123+45_1123+46delCT (chr6-33195860-AAG-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_021976.5(RXRB):c.1123+45_1123+46delCT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0534 in 1,610,020 control chromosomes in the GnomAD database, including 4,565 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.10 ( 1533 hom., cov: 31)

Exomes 𝑓: 0.048 ( 3032 hom. )

Consequence

RXRB
NM_021976.5 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.19

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 -8 ACMG points.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.257 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RXRB	NM_021976.5 link	c.1123+45_1123+46delCT		intron_variant	Intron 6 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.1123+45_1123+46delCT	intron_variant	Intron 6 of 9	1	NM_021976.5	ENSP00000363812.3	P28702-1
RXRB	ENST00000374685.8 link	c.1123+45_1123+46delCT	intron_variant	Intron 6 of 9	1		ENSP00000363817.4	P28702-3
RXRB	ENST00000481441.1 link	n.1253_1254delCT	non_coding_transcript_exon_variant	Exon 3 of 3	2
RXRB	ENST00000483281.5 link	n.635+45_635+46delCT	intron_variant	Intron 5 of 8	5		ENSP00000431369.1	E9PK75

Frequencies

GnomAD3 genomes

AF:

0.103

AC:

15616

AN:

151998

Hom.:

1530

Cov.:

show subpopulations

Gnomad AFR

AF:

0.262

Gnomad AMI

AF:

0.0208

Gnomad AMR

AF:

0.0516

Gnomad ASJ

AF:

0.00951

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00228

Gnomad FIN

AF:

0.0489

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0478

Gnomad OTH

AF:

0.0876

GnomAD2 exomes

AF:

0.0454

AC:

11171

AN:

245970

AF XY:

0.0397

show subpopulations

Gnomad AFR exome

AF:

0.275

Gnomad AMR exome

AF:

0.0248

Gnomad ASJ exome

AF:

0.00937

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0504

Gnomad NFE exome

AF:

0.0431

Gnomad OTH exome

AF:

0.0328

GnomAD4 exome

AF:

0.0483

AC:

70352

AN:

1457904

Hom.:

3032

AF XY:

0.0458

AC XY:

33228

AN XY:

725008

show subpopulations

African (AFR)

AF:

0.291

AC:

9723

AN:

33410

American (AMR)

AF:

0.0285

AC:

1272

AN:

44706

Ashkenazi Jewish (ASJ)

AF:

0.00874

AC:

228

AN:

26092

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39664

South Asian (SAS)

AF:

0.00149

AC:

128

AN:

86168

European-Finnish (FIN)

AF:

0.0505

AC:

2633

AN:

52138

Middle Eastern (MID)

AF:

0.0191

AC:

AN:

4558

European-Non Finnish (NFE)

AF:

0.0482

AC:

53524

AN:

1110946

Other (OTH)

AF:

0.0458

AC:

2756

AN:

60222

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

3418

6836

10254

13672

17090

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.103

AC:

15637

AN:

152116

Hom.:

1533

Cov.:

AF XY:

0.0985

AC XY:

7330

AN XY:

74406

show subpopulations

African (AFR)

AF:

0.262

AC:

10829

AN:

41410

American (AMR)

AF:

0.0515

AC:

788

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00951

AC:

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5182

South Asian (SAS)

AF:

0.00228

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.0489

AC:

518

AN:

10602

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0478

AC:

3254

AN:

68010

Other (OTH)

AF:

0.0866

AC:

183

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

596

1192

1788

2384

2980

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0682

Hom.:

144

Bravo

AF:

0.111

Asia WGS

AF:

0.0160

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.2

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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chr6-33195860-AAG-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over