dbSNP rs2276014: ESRRA:p.Pro116Pro (chr11-64313973-G-A) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_ModerateBP7BA1

The NM_004451.5(ESRRA):c.348G>A(p.Pro116Pro) 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

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.171

Publications

21 publications found

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]

ESRRA links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
ESRRA	NM_004451.5 link	c.348G>A	p.Pro116Pro	synonymous_variant	Exon 3 of 7	ENST00000000442.11	NP_004442.3	P11474-1Q569H8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ESRRA	ENST00000000442.11 link	c.348G>A	p.Pro116Pro	synonymous_variant	Exon 3 of 7	1	NM_004451.5	ENSP00000000442.6		P11474-1

Frequencies

GnomAD3 genomes

AF:

0.120

AC:

18204

AN:

152114

Hom.:

1388

Cov.:

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

GnomAD2 exomes

AF:

0.131

AC:

25654

AN:

195124

AF XY:

0.134

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 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.:

AF XY:

0.150

AC XY:

105921

AN XY:

706530

show subpopulations

African (AFR)

AF:

0.0373

AC:

1223

AN:

32774

American (AMR)

AF:

0.108

AC:

4304

AN:

39824

Ashkenazi Jewish (ASJ)

AF:

0.127

AC:

3234

AN:

25486

East Asian (EAS)

AF:

0.104

AC:

3959

AN:

38052

South Asian (SAS)

AF:

0.0845

AC:

6950

AN:

82202

European-Finnish (FIN)

AF:

0.159

AC:

8018

AN:

50482

Middle Eastern (MID)

AF:

0.178

AC:

840

AN:

4732

European-Non Finnish (NFE)

AF:

0.162

AC:

177332

AN:

1094048

Other (OTH)

AF:

0.153

AC:

9007

AN:

58914

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

8240

16479

24719

32958

41198

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6226

12452

18678

24904

31130

<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:

0.120

AC:

18207

AN:

152232

Hom.:

1387

Cov.:

AF XY:

0.119

AC XY:

8876

AN XY:

74424

show subpopulations

African (AFR)

AF:

0.0430

AC:

1786

AN:

41556

American (AMR)

AF:

0.129

AC:

1976

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.117

AC:

405

AN:

3472

East Asian (EAS)

AF:

0.110

AC:

567

AN:

5170

South Asian (SAS)

AF:

0.0717

AC:

346

AN:

4824

European-Finnish (FIN)

AF:

0.164

AC:

1735

AN:

10596

Middle Eastern (MID)

AF:

0.163

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.161

AC:

10919

AN:

67986

Other (OTH)

AF:

0.155

AC:

328

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

829

1658

2488

3317

4146

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

200

400

600

800

1000

<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:

0.124

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

(source)

DANN

Benign

0.93

PhyloP100

-0.17

PromoterAI

0.033

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=97/3

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over