Genetic Variant RXRA:c.*3851T>G (chr9-134440465-T-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_002957.6(RXRA):c.*3851T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.861 in 152,684 control chromosomes in the GnomAD database, including 56,832 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 0.86 ( 56712 hom., cov: 35)

Exomes 𝑓: 0.81 ( 120 hom. )

Consequence

RXRA
NM_002957.6 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.605

Publications

34 publications found

Variant links:

COSMIC-nc: COSV62683924

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=-0.9).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.953 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.*3851T>G	3_prime_UTR	Exon 10 of 10	NP_002948.1	P19793-1
RXRA	NM_001291920.2		c.*3851T>G	3_prime_UTR	Exon 10 of 10	NP_001278849.1	A0A5F9ZHH6
RXRA	NM_001291921.2		c.*3851T>G	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.*3851T>G		3_prime_UTR	Exon 10 of 10	ENSP00000419692.1	P19793-1
	RXRA	ENST00000356384.4	TSL:5	n.5650T>G		non_coding_transcript_exon	Exon 12 of 12

Frequencies

GnomAD3 genomes

AF:

0.861

AC:

130994

AN:

152198

Hom.:

56670

Cov.:

show subpopulations

Gnomad AFR

AF:

0.961

Gnomad AMI

AF:

0.900

Gnomad AMR

AF:

0.817

Gnomad ASJ

AF:

0.816

Gnomad EAS

AF:

0.825

Gnomad SAS

AF:

0.690

Gnomad FIN

AF:

0.828

Gnomad MID

AF:

0.826

Gnomad NFE

AF:

0.832

Gnomad OTH

AF:

0.845

GnomAD4 exome

AF:

0.813

AC:

299

AN:

368

Hom.:

120

Cov.:

AF XY:

0.812

AC XY:

177

AN XY:

218

show subpopulations

African (AFR)

AF:

1.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

1.00

AC:

AN:

East Asian (EAS)

AF:

0.750

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.807

AC:

239

AN:

296

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.804

AC:

AN:

Other (OTH)

AF:

1.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.516

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:

0.861

AC:

131093

AN:

152316

Hom.:

56712

Cov.:

AF XY:

0.857

AC XY:

63802

AN XY:

74472

show subpopulations

African (AFR)

AF:

0.961

AC:

39943

AN:

41574

American (AMR)

AF:

0.817

AC:

12499

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.816

AC:

2832

AN:

3472

East Asian (EAS)

AF:

0.825

AC:

4279

AN:

5188

South Asian (SAS)

AF:

0.689

AC:

3328

AN:

4832

European-Finnish (FIN)

AF:

0.828

AC:

8781

AN:

10610

Middle Eastern (MID)

AF:

0.827

AC:

243

AN:

294

European-Non Finnish (NFE)

AF:

0.832

AC:

56594

AN:

68026

Other (OTH)

AF:

0.841

AC:

1773

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

955

1910

2864

3819

4774

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

890

1780

2670

3560

4450

<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:

0.841

Hom.:

78753

Bravo

AF:

0.867

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.041

(source)

DANN

Benign

0.54

PhyloP100

-0.60

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