dbSNP rs875444: RXRA:c.279+1576G>A (chr9-134403458-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.279+1576G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.467 in 152,234 control chromosomes in the GnomAD database, including 19,346 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 0.47 ( 19334 hom., cov: 35)

Exomes 𝑓: 0.58 ( 12 hom. )

Consequence

RXRA
NM_002957.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.305

Publications

11 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=-0.9).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.599 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RXRA	NM_002957.6	MANE Select	c.279+1576G>A		intron	N/A	NP_002948.1	P19793-1
	RXRA	NM_001291920.2		c.198+1576G>A		intron	N/A	NP_001278849.1	A0A5F9ZHH6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
RXRA	ENST00000481739.2	TSL:1 MANE Select	c.279+1576G>A	intron	N/A	ENSP00000419692.1	P19793-1
RXRA	ENST00000672570.1		c.198+1576G>A	intron	N/A	ENSP00000500402.1	A0A5F9ZHH6
RXRA	ENST00000484822.1	TSL:2	n.2279G>A	non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes

AF:

0.467

AC:

71030

AN:

152056

Hom.:

19337

Cov.:

show subpopulations

Gnomad AFR

AF:

0.169

Gnomad AMI

AF:

0.607

Gnomad AMR

AF:

0.514

Gnomad ASJ

AF:

0.573

Gnomad EAS

AF:

0.599

Gnomad SAS

AF:

0.436

Gnomad FIN

AF:

0.582

Gnomad MID

AF:

0.503

Gnomad NFE

AF:

0.604

Gnomad OTH

AF:

0.504

GnomAD4 exome

AF:

0.583

AC:

AN:

Hom.:

Cov.:

AF XY:

0.605

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.500

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.750

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.643

AC:

AN:

Other (OTH)

AF:

0.667

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.543

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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:

0.467

AC:

71019

AN:

152174

Hom.:

19334

Cov.:

AF XY:

0.467

AC XY:

34778

AN XY:

74392

show subpopulations

African (AFR)

AF:

0.168

AC:

6998

AN:

41544

American (AMR)

AF:

0.515

AC:

7875

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.573

AC:

1990

AN:

3472

East Asian (EAS)

AF:

0.598

AC:

3083

AN:

5154

South Asian (SAS)

AF:

0.436

AC:

2104

AN:

4824

European-Finnish (FIN)

AF:

0.582

AC:

6160

AN:

10592

Middle Eastern (MID)

AF:

0.507

AC:

149

AN:

294

European-Non Finnish (NFE)

AF:

0.604

AC:

41052

AN:

67966

Other (OTH)

AF:

0.500

AC:

1054

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1749

3497

5246

6994

8743

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

632

1264

1896

2528

3160

<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:

0.550

Hom.:

31929

Bravo

AF:

0.452

Asia WGS

AF:

0.496

AC:

1726

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

2.1

(source)

DANN

Benign

0.68

PhyloP100

-0.30

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