dbSNP rs34449651: RXRA:c.*953G>C (chr9-134437567-G-C) – 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.*953G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0109 in 152,424 control chromosomes in the GnomAD database, including 27 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 0.011 ( 27 hom., cov: 33)

Exomes 𝑓: 0.0060 ( 0 hom. )

Consequence

RXRA
NM_002957.6 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0100

Publications

1 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

new If you want to explore the variant's impact on the transcript NM_002957.6, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

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=-0.91).

BA1

GnomAdExome4 highest subpopulation (AFR) allele frequency = 0.5 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.*953G>C	3_prime_UTR	Exon 10 of 10	NP_002948.1	P19793-1
RXRA	NM_001291920.2		c.*953G>C	3_prime_UTR	Exon 10 of 10	NP_001278849.1	A0A5F9ZHH6
RXRA	NM_001291921.2		c.*953G>C	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.*953G>C		3_prime_UTR	Exon 10 of 10	ENSP00000419692.1	P19793-1
	RXRA	ENST00000356384.4	TSL:5	n.2752G>C		non_coding_transcript_exon	Exon 12 of 12

Frequencies

GnomAD3 genomes

AF:

0.0108

AC:

1645

AN:

152140

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0375

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00419

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000206

Gnomad OTH

AF:

0.00574

GnomAD4 exome

AF:

0.00602

AC:

AN:

166

Hom.:

Cov.:

AF XY:

0.00735

AC XY:

AN XY:

136

show subpopulations

African (AFR)

AF:

0.500

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

102

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0109

AC:

1653

AN:

152258

Hom.:

Cov.:

AF XY:

0.0104

AC XY:

775

AN XY:

74436

show subpopulations

African (AFR)

AF:

0.0376

AC:

1562

AN:

41550

American (AMR)

AF:

0.00418

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3464

East Asian (EAS)

AF:

0.00

AC:

AN:

5152

South Asian (SAS)

AF:

0.000207

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000206

AC:

AN:

68018

Other (OTH)

AF:

0.00568

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

164

247

329

411

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00867

Hom.:

Bravo

AF:

0.0126

Asia WGS

AF:

0.00231

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.57

(source)

DANN

Benign

0.43

PhyloP100

0.010

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over