Genetic Variant RXRA:c.*846G>A (chr9-134437460-G-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.*846G>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 0.544 in 152,502 control chromosomes in the GnomAD database, including 24,417 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 0.54 ( 24301 hom., cov: 33)

Exomes 𝑓: 0.65 ( 116 hom. )

Consequence

RXRA
NM_002957.6 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.109

Publications

15 publications found

Variant links:

COSMIC-nc: COSV62683920

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=-0.83).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.65 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.*846G>A	3_prime_UTR	Exon 10 of 10	NP_002948.1	P19793-1
RXRA	NM_001291920.2		c.*846G>A	3_prime_UTR	Exon 10 of 10	NP_001278849.1	A0A5F9ZHH6
RXRA	NM_001291921.2		c.*846G>A	3_prime_UTR	Exon 9 of 9	NP_001278850.1	P19793-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RXRA	ENST00000481739.2	TSL:1 MANE Select	c.*846G>A		3_prime_UTR	Exon 10 of 10	ENSP00000419692.1	P19793-1
	RXRA	ENST00000356384.4	TSL:5	n.2645G>A		non_coding_transcript_exon	Exon 12 of 12

Frequencies

GnomAD3 genomes

AF:

0.544

AC:

82569

AN:

151870

Hom.:

24301

Cov.:

show subpopulations

Gnomad AFR

AF:

0.303

Gnomad AMI

AF:

0.657

Gnomad AMR

AF:

0.579

Gnomad ASJ

AF:

0.643

Gnomad EAS

AF:

0.657

Gnomad SAS

AF:

0.491

Gnomad FIN

AF:

0.642

Gnomad MID

AF:

0.544

Gnomad NFE

AF:

0.655

Gnomad OTH

AF:

0.572

GnomAD4 exome

AF:

0.652

AC:

335

AN:

514

Hom.:

116

Cov.:

AF XY:

0.678

AC XY:

240

AN XY:

354

show subpopulations

African (AFR)

AF:

0.0833

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.500

AC:

AN:

East Asian (EAS)

AF:

0.714

AC:

AN:

South Asian (SAS)

AF:

0.667

AC:

AN:

European-Finnish (FIN)

AF:

0.614

AC:

AN:

140

Middle Eastern (MID)

AF:

0.333

AC:

AN:

European-Non Finnish (NFE)

AF:

0.701

AC:

223

AN:

318

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.543

AC:

82579

AN:

151988

Hom.:

24301

Cov.:

AF XY:

0.545

AC XY:

40475

AN XY:

74296

show subpopulations

African (AFR)

AF:

0.302

AC:

12548

AN:

41486

American (AMR)

AF:

0.579

AC:

8849

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.643

AC:

2231

AN:

3468

East Asian (EAS)

AF:

0.657

AC:

3368

AN:

5128

South Asian (SAS)

AF:

0.489

AC:

2356

AN:

4814

European-Finnish (FIN)

AF:

0.642

AC:

6797

AN:

10580

Middle Eastern (MID)

AF:

0.554

AC:

163

AN:

294

European-Non Finnish (NFE)

AF:

0.655

AC:

44475

AN:

67922

Other (OTH)

AF:

0.566

AC:

1195

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

1767

3535

5302

7070

8837

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

708

1416

2124

2832

3540

<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:

0.614

Hom.:

39948

Bravo

AF:

0.531

Asia WGS

AF:

0.565

AC:

1967

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

2.2

(source)

DANN

Benign

0.78

PhyloP100

-0.11

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

0.98

Splicing

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