Genetic Variant NM_004451.5:c.1012+65C>T (chr11-64315335-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_004451.5(ESRRA):c.1012+65C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.149 in 1,476,794 control chromosomes in the GnomAD database, including 17,438 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 ( 1390 hom., cov: 34)

Exomes 𝑓: 0.15 ( 16048 hom. )

Consequence

ESRRA
NM_004451.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.252

Publications

29 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

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.1012+65C>T		intron_variant	Intron 6 of 6	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.1012+65C>T		intron_variant	Intron 6 of 6	1	NM_004451.5	ENSP00000000442.6		P11474-1

Frequencies

GnomAD3 genomes

AF:

0.120

AC:

18217

AN:

152154

Hom.:

1391

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0430

Gnomad AMI

AF:

0.106

Gnomad AMR

AF:

0.129

Gnomad ASJ

AF:

0.117

Gnomad EAS

AF:

0.111

Gnomad SAS

AF:

0.0714

Gnomad FIN

AF:

0.163

Gnomad MID

AF:

0.158

Gnomad NFE

AF:

0.161

Gnomad OTH

AF:

0.151

GnomAD4 exome

AF:

0.153

AC:

202279

AN:

1324522

Hom.:

16048

AF XY:

0.152

AC XY:

98547

AN XY:

647694

show subpopulations

African (AFR)

AF:

0.0363

AC:

1074

AN:

29556

American (AMR)

AF:

0.114

AC:

2957

AN:

26040

Ashkenazi Jewish (ASJ)

AF:

0.127

AC:

2452

AN:

19324

East Asian (EAS)

AF:

0.104

AC:

3967

AN:

38044

South Asian (SAS)

AF:

0.0850

AC:

5741

AN:

67564

European-Finnish (FIN)

AF:

0.159

AC:

7539

AN:

47422

Middle Eastern (MID)

AF:

0.181

AC:

937

AN:

5176

European-Non Finnish (NFE)

AF:

0.163

AC:

169220

AN:

1036590

Other (OTH)

AF:

0.153

AC:

8392

AN:

54806

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

8610

17221

25831

34442

43052

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6110

12220

18330

24440

30550

<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:

18220

AN:

152272

Hom.:

1390

Cov.:

AF XY:

0.119

AC XY:

8884

AN XY:

74450

show subpopulations

African (AFR)

AF:

0.0429

AC:

1783

AN:

41570

American (AMR)

AF:

0.129

AC:

1975

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.117

AC:

405

AN:

3472

East Asian (EAS)

AF:

0.110

AC:

571

AN:

5176

South Asian (SAS)

AF:

0.0718

AC:

347

AN:

4830

European-Finnish (FIN)

AF:

0.163

AC:

1730

AN:

10602

Middle Eastern (MID)

AF:

0.163

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.161

AC:

10935

AN:

68006

Other (OTH)

AF:

0.156

AC:

329

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

820

1640

2460

3280

4100

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

202

404

606

808

1010

<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:

0.146

Hom.:

5554

Bravo

AF:

0.115

Asia WGS

AF:

0.116

AC:

401

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

2.1

(source)

DANN

Benign

0.73

PhyloP100

-0.25

Mutation Taster

=100/0

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