dbSNP rs1805352: RXRA:c.280-46C>A (chr9-134408103-C-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_002957.6(RXRA):c.280-46C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.66 in 1,460,986 control chromosomes in the GnomAD database, including 324,488 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 0.58 ( 27290 hom., cov: 30)

Exomes 𝑓: 0.67 ( 297198 hom. )

Consequence

RXRA
NM_002957.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.60

Publications

30 publications found

Variant links:

Genes affected

RXRA (HGNC:10477): (retinoid X receptor alpha) Retinoid X receptors (RXRs) and retinoic acid receptors (RARs) are nuclear receptors that mediate the biological effects of retinoids by their involvement in retinoic acid-mediated gene activation. These receptors function as transcription factors by binding as homodimers or heterodimers to specific sequences in the promoters of target genes. The protein encoded by this gene is a member of the steroid and thyroid hormone receptor superfamily of transcriptional regulators. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, May 2014]

RXRA Gene-Disease associations (from GenCC):

congenital heart disease
Inheritance: Unknown Classification: NO_KNOWN Submitted by: ClinGen

RXRA links:

Genome browser will be placed here

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=-0.8).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.739 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002957.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
RXRA	NM_002957.6	MANE Select	c.280-46C>A	intron	N/A	NP_002948.1	P19793-1
RXRA	NM_001291920.2		c.199-46C>A	intron	N/A	NP_001278849.1	A0A5F9ZHH6
RXRA	NM_001291921.2		c.-12-46C>A	intron	N/A	NP_001278850.1	P19793-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
RXRA	ENST00000481739.2	TSL:1 MANE Select	c.280-46C>A	intron	N/A	ENSP00000419692.1	P19793-1
RXRA	ENST00000672570.1		c.199-46C>A	intron	N/A	ENSP00000500402.1	A0A5F9ZHH6
RXRA	ENST00000356384.4	TSL:5	n.690-46C>A	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.579

AC:

87649

AN:

151414

Hom.:

27290

Cov.:

show subpopulations

Gnomad AFR

AF:

0.330

Gnomad AMI

AF:

0.748

Gnomad AMR

AF:

0.629

Gnomad ASJ

AF:

0.672

Gnomad EAS

AF:

0.759

Gnomad SAS

AF:

0.476

Gnomad FIN

AF:

0.691

Gnomad MID

AF:

0.598

Gnomad NFE

AF:

0.686

Gnomad OTH

AF:

0.621

GnomAD2 exomes

AF:

0.630

AC:

94536

AN:

149996

AF XY:

0.634

show subpopulations

Gnomad AFR exome

AF:

0.317

Gnomad AMR exome

AF:

0.617

Gnomad ASJ exome

AF:

0.681

Gnomad EAS exome

AF:

0.751

Gnomad FIN exome

AF:

0.691

Gnomad NFE exome

AF:

0.680

Gnomad OTH exome

AF:

0.646

GnomAD4 exome

AF:

0.669

AC:

876005

AN:

1309454

Hom.:

297198

Cov.:

AF XY:

0.664

AC XY:

426881

AN XY:

642824

show subpopulations

African (AFR)

AF:

0.308

AC:

8691

AN:

28258

American (AMR)

AF:

0.625

AC:

15074

AN:

24114

Ashkenazi Jewish (ASJ)

AF:

0.690

AC:

13121

AN:

19026

East Asian (EAS)

AF:

0.757

AC:

25961

AN:

34308

South Asian (SAS)

AF:

0.475

AC:

31107

AN:

65506

European-Finnish (FIN)

AF:

0.690

AC:

33160

AN:

48090

Middle Eastern (MID)

AF:

0.618

AC:

3198

AN:

5176

European-Non Finnish (NFE)

AF:

0.689

AC:

710545

AN:

1031232

Other (OTH)

AF:

0.654

AC:

35148

AN:

53744

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

12362

24724

37086

49448

61810

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18732

37464

56196

74928

93660

<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:

0.579

AC:

87672

AN:

151532

Hom.:

27290

Cov.:

AF XY:

0.580

AC XY:

42926

AN XY:

74024

show subpopulations

African (AFR)

AF:

0.330

AC:

13585

AN:

41164

American (AMR)

AF:

0.630

AC:

9620

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.672

AC:

2329

AN:

3468

East Asian (EAS)

AF:

0.759

AC:

3864

AN:

5094

South Asian (SAS)

AF:

0.476

AC:

2287

AN:

4806

European-Finnish (FIN)

AF:

0.691

AC:

7295

AN:

10558

Middle Eastern (MID)

AF:

0.609

AC:

179

AN:

294

European-Non Finnish (NFE)

AF:

0.686

AC:

46542

AN:

67862

Other (OTH)

AF:

0.615

AC:

1293

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

1666

3332

4999

6665

8331

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

726

1452

2178

2904

3630

<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:

0.648

Hom.:

31763

Bravo

AF:

0.568

Asia WGS

AF:

0.601

AC:

2092

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.074

(source)

DANN

Benign

0.40

PhyloP100

-1.6

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