dbSNP rs4842194: RXRA:c.*2100C>T (chr9-134438714-C-T) – 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.*2100C>T 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 153,130 control chromosomes in the GnomAD database, including 24,567 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 ( 24391 hom., cov: 35)

Exomes 𝑓: 0.61 ( 176 hom. )

Consequence

RXRA
NM_002957.6 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.243

Publications

16 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 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=-0.72).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.65 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
RXRA	NM_002957.6 link	c.*2100C>T	3_prime_UTR_variant	Exon 10 of 10	ENST00000481739.2	NP_002948.1
RXRA	NM_001291920.2 link	c.*2100C>T	3_prime_UTR_variant	Exon 10 of 10		NP_001278849.1
RXRA	NM_001291921.2 link	c.*2100C>T	3_prime_UTR_variant	Exon 9 of 9		NP_001278850.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RXRA	ENST00000481739.2 link	c.*2100C>T		3_prime_UTR_variant	Exon 10 of 10	1	NM_002957.6	ENSP00000419692.1
RXRA	ENST00000356384.4 link	n.3899C>T		non_coding_transcript_exon_variant	Exon 12 of 12	5

Frequencies

GnomAD3 genomes

AF:

0.544

AC:

82762

AN:

152106

Hom.:

24391

Cov.:

show subpopulations

Gnomad AFR

AF:

0.302

Gnomad AMI

AF:

0.655

Gnomad AMR

AF:

0.581

Gnomad ASJ

AF:

0.644

Gnomad EAS

AF:

0.656

Gnomad SAS

AF:

0.495

Gnomad FIN

AF:

0.641

Gnomad MID

AF:

0.547

Gnomad NFE

AF:

0.656

Gnomad OTH

AF:

0.572

GnomAD4 exome

AF:

0.615

AC:

557

AN:

906

Hom.:

176

Cov.:

AF XY:

0.622

AC XY:

311

AN XY:

500

show subpopulations

African (AFR)

AF:

0.200

AC:

AN:

American (AMR)

AF:

0.500

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.667

AC:

AN:

East Asian (EAS)

AF:

0.662

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.641

AC:

259

AN:

404

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.609

AC:

212

AN:

348

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

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:

0.544

AC:

82771

AN:

152224

Hom.:

24391

Cov.:

AF XY:

0.545

AC XY:

40581

AN XY:

74412

show subpopulations

African (AFR)

AF:

0.302

AC:

12552

AN:

41540

American (AMR)

AF:

0.581

AC:

8888

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.644

AC:

2234

AN:

3470

East Asian (EAS)

AF:

0.656

AC:

3389

AN:

5166

South Asian (SAS)

AF:

0.494

AC:

2387

AN:

4832

European-Finnish (FIN)

AF:

0.641

AC:

6791

AN:

10600

Middle Eastern (MID)

AF:

0.558

AC:

164

AN:

294

European-Non Finnish (NFE)

AF:

0.656

AC:

44574

AN:

67994

Other (OTH)

AF:

0.566

AC:

1195

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1808

3616

5425

7233

9041

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

710

1420

2130

2840

3550

<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:

0.509

Hom.:

2434

Bravo

AF:

0.532

Asia WGS

AF:

0.567

AC:

1975

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.72

CADD

Benign

8.0

(source)

DANN

Benign

0.94

PhyloP100

0.24

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over