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GeneBe

9-134401726-C-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2

The NM_002957.6(RXRA):c.123C>T(p.Ile41=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00134 in 1,613,162 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00085 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0014 ( 0 hom. )

Consequence

RXRA
NM_002957.6 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0340
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.39).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 9-134401726-C-T is Benign according to our data. Variant chr9-134401726-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 735059.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-0.034 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 130 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RXRANM_002957.6 linkuse as main transcriptc.123C>T p.Ile41= synonymous_variant 2/10 ENST00000481739.2
RXRANM_001291920.2 linkuse as main transcriptc.42C>T p.Ile14= synonymous_variant 2/10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RXRAENST00000481739.2 linkuse as main transcriptc.123C>T p.Ile41= synonymous_variant 2/101 NM_002957.6 P3P19793-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000854
AC:
130
AN:
152200
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000265
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000578
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00151
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00146
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000977
AC:
244
AN:
249804
Hom.:
0
AF XY:
0.000960
AC XY:
130
AN XY:
135466
show subpopulations
Gnomad AFR exome
AF:
0.000372
Gnomad AMR exome
AF:
0.000202
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000327
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00189
Gnomad NFE exome
AF:
0.00159
Gnomad OTH exome
AF:
0.000817
GnomAD4 exome
AF:
0.00139
AC:
2025
AN:
1460844
Hom.:
0
Cov.:
32
AF XY:
0.00131
AC XY:
952
AN XY:
726754
show subpopulations
Gnomad4 AFR exome
AF:
0.000179
Gnomad4 AMR exome
AF:
0.000179
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000176
Gnomad4 SAS exome
AF:
0.0000348
Gnomad4 FIN exome
AF:
0.00208
Gnomad4 NFE exome
AF:
0.00163
Gnomad4 OTH exome
AF:
0.00123
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000853
AC:
130
AN:
152318
Hom.:
0
Cov.:
33
AF XY:
0.000792
AC XY:
59
AN XY:
74470
show subpopulations
Gnomad4 AFR
AF:
0.000265
Gnomad4 AMR
AF:
0.0000653
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000580
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00151
Gnomad4 NFE
AF:
0.00146
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.00139
Hom.:
2
Bravo
AF:
0.000752
EpiCase
AF:
0.00125
EpiControl
AF:
0.00107

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingInvitaeJul 17, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.39
Cadd
Benign
6.2
Dann
Benign
0.80
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1805337; hg19: chr9-137293572; API