rs2276014

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_ModerateBP7BA1

The NM_004451.5(ESRRA):​c.348G>A​(p.Pro116=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.148 in 1,578,746 control chromosomes in the GnomAD database, including 18,325 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 0.12 ( 1387 hom., cov: 33)
Exomes 𝑓: 0.15 ( 16938 hom. )

Consequence

ESRRA
NM_004451.5 synonymous

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.171
Variant links:
Genes affected
ESRRA (HGNC:3471): (estrogen related receptor alpha) The protein encoded by this gene is a nuclear receptor that is most closely related to the estrogen receptor. This protein acts as a site-specific transcription factor and interacts with members of the PGC-1 family of transcription cofactors to regulate the expression of most genes involved in cellular energy production as well as in the process of mitochondrial biogenesis. A processed pseudogene of ESRRA is located on chromosome 13q12.1. [provided by RefSeq, Jun 2019]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.46).
BP7
Synonymous conserved (PhyloP=-0.171 with no splicing effect.
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.158 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ESRRANM_004451.5 linkuse as main transcriptc.348G>A p.Pro116= synonymous_variant 3/7 ENST00000000442.11

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ESRRAENST00000000442.11 linkuse as main transcriptc.348G>A p.Pro116= synonymous_variant 3/71 NM_004451.5 P4P11474-1

Frequencies

GnomAD3 genomes
AF:
0.120
AC:
18204
AN:
152114
Hom.:
1388
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0431
Gnomad AMI
AF:
0.106
Gnomad AMR
AF:
0.129
Gnomad ASJ
AF:
0.117
Gnomad EAS
AF:
0.110
Gnomad SAS
AF:
0.0713
Gnomad FIN
AF:
0.164
Gnomad MID
AF:
0.158
Gnomad NFE
AF:
0.161
Gnomad OTH
AF:
0.151
GnomAD3 exomes
AF:
0.131
AC:
25654
AN:
195124
Hom.:
1865
AF XY:
0.134
AC XY:
14180
AN XY:
105618
show subpopulations
Gnomad AFR exome
AF:
0.0399
Gnomad AMR exome
AF:
0.108
Gnomad ASJ exome
AF:
0.124
Gnomad EAS exome
AF:
0.110
Gnomad SAS exome
AF:
0.0874
Gnomad FIN exome
AF:
0.158
Gnomad NFE exome
AF:
0.163
Gnomad OTH exome
AF:
0.153
GnomAD4 exome
AF:
0.151
AC:
214867
AN:
1426514
Hom.:
16938
Cov.:
32
AF XY:
0.150
AC XY:
105921
AN XY:
706530
show subpopulations
Gnomad4 AFR exome
AF:
0.0373
Gnomad4 AMR exome
AF:
0.108
Gnomad4 ASJ exome
AF:
0.127
Gnomad4 EAS exome
AF:
0.104
Gnomad4 SAS exome
AF:
0.0845
Gnomad4 FIN exome
AF:
0.159
Gnomad4 NFE exome
AF:
0.162
Gnomad4 OTH exome
AF:
0.153
GnomAD4 genome
AF:
0.120
AC:
18207
AN:
152232
Hom.:
1387
Cov.:
33
AF XY:
0.119
AC XY:
8876
AN XY:
74424
show subpopulations
Gnomad4 AFR
AF:
0.0430
Gnomad4 AMR
AF:
0.129
Gnomad4 ASJ
AF:
0.117
Gnomad4 EAS
AF:
0.110
Gnomad4 SAS
AF:
0.0717
Gnomad4 FIN
AF:
0.164
Gnomad4 NFE
AF:
0.161
Gnomad4 OTH
AF:
0.155
Alfa
AF:
0.124
Hom.:
616
Bravo
AF:
0.115
Asia WGS
AF:
0.115
AC:
399
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.46
CADD
Benign
10
DANN
Benign
0.93
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: rs2276014; hg19: chr11-64081445; COSMIC: COSV50005850; COSMIC: COSV50005850; API