Variant 11-64307271-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_004451.5(ESRRA):c.92C>T(p.Thr31Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00354 in 1,613,494 control chromosomes in the GnomAD database, including 20 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0047 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0034 ( 17 hom. )

Consequence

ESRRA
NM_004451.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.886

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 made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004929304).

BP6

Variant 11-64307271-C-T is Benign according to our data. Variant chr11-64307271-C-T is described in ClinVar as [Benign]. Clinvar id is 789313.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ESRRA	NM_004451.5 linkuse as main transcript	c.92C>T	p.Thr31Ile	missense_variant	2/7	ENST00000000442.11	NP_004442.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ESRRA	ENST00000000442.11 linkuse as main transcript	c.92C>T	p.Thr31Ile	missense_variant	2/7	1	NM_004451.5	ENSP00000000442	P4	P11474-1

Frequencies

GnomAD3 genomes

AF:

0.00474

AC:

721

AN:

152224

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00880

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00667

Gnomad ASJ

AF:

0.00317

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.000282

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.00313

Gnomad OTH

AF:

0.00956

GnomAD3 exomes

AF:

0.00334

AC:

824

AN:

246350

Hom.:

AF XY:

0.00323

AC XY:

433

AN XY:

134098

show subpopulations

Gnomad AFR exome

AF:

0.00914

Gnomad AMR exome

AF:

0.00482

Gnomad ASJ exome

AF:

0.00449

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000818

Gnomad FIN exome

AF:

0.000510

Gnomad NFE exome

AF:

0.00374

Gnomad OTH exome

AF:

0.00382

GnomAD4 exome

AF:

0.00342

AC:

4998

AN:

1461152

Hom.:

Cov.:

AF XY:

0.00330

AC XY:

2398

AN XY:

726888

show subpopulations

Gnomad4 AFR exome

AF:

0.00828

Gnomad4 AMR exome

AF:

0.00470

Gnomad4 ASJ exome

AF:

0.00387

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000952

Gnomad4 FIN exome

AF:

0.000600

Gnomad4 NFE exome

AF:

0.00357

Gnomad4 OTH exome

AF:

0.00469

GnomAD4 genome

AF:

0.00472

AC:

719

AN:

152342

Hom.:

Cov.:

AF XY:

0.00462

AC XY:

344

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.00878

Gnomad4 AMR

AF:

0.00666

Gnomad4 ASJ

AF:

0.00317

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.000282

Gnomad4 NFE

AF:

0.00313

Gnomad4 OTH

AF:

0.00946

Alfa

AF:

0.00392

Hom.:

Bravo

AF:

0.00521

TwinsUK

AF:

0.00593

AC:

ALSPAC

AF:

0.00441

AC:

ESP6500AA

AF:

0.00778

AC:

ESP6500EA

AF:

0.00310

AC:

ExAC

AF:

0.00329

AC:

398

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.00414

EpiControl

AF:

0.00522

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.17

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.11

.;T;T;T

Eigen

Benign

-0.36

Eigen_PC

Benign

-0.22

FATHMM_MKL

Uncertain

0.76

LIST_S2

Benign

0.79

T;.;T;T

M_CAP

Benign

0.067

MetaRNN

Benign

0.0049

T;T;T;T

MetaSVM

Uncertain

-0.26

MutationAssessor

Benign

0.34

N;N;N;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Uncertain

0.62

PROVEAN

Benign

-0.75

N;N;N;N

REVEL

Benign

0.23

Sift

Benign

0.39

T;T;T;T

Sift4G

Benign

0.19

T;T;T;T

Polyphen

0.0

B;P;P;.

Vest4

0.36

MVP

0.72

MPC

0.67

ClinPred

0.0055

GERP RS

4.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.10

gMVP

0.25

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over