Genetic Variant EGR3:p.Leu120Leu (chr8-22691277-G-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_004430.3(EGR3):c.360C>A(p.Leu120Leu) variant causes a synonymous change. The variant allele was found at a frequency of 0.0827 in 1,613,898 control chromosomes in the GnomAD database, including 6,278 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.085 ( 578 hom., cov: 33)

Exomes 𝑓: 0.082 ( 5700 hom. )

Consequence

EGR3
NM_004430.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 3.77

Publications

16 publications found

Variant links:

Genes affected

EGR3 (HGNC:3240): (early growth response 3) This gene encodes a transcriptional regulator that belongs to the EGR family of C2H2-type zinc-finger proteins. It is an immediate-early growth response gene which is induced by mitogenic stimulation. The protein encoded by this gene participates in the transcriptional regulation of genes in controling biological rhythm. It may also play a role in a wide variety of processes including muscle development, lymphocyte development, endothelial cell growth and migration, and neuronal development. Alternative splicing results in multiple transcript variants encoding distinct isoforms.[provided by RefSeq, Dec 2010]

EGR3 links:

ENSG00000253125 (HGNC:58186):

ENSG00000253125 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.65).

BP6

Variant 8-22691277-G-T is Benign according to our data. Variant chr8-22691277-G-T is described in ClinVar as Benign. ClinVar VariationId is 1287186.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.195 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EGR3	NM_004430.3 link	c.360C>A	p.Leu120Leu	synonymous_variant	Exon 2 of 2	ENST00000317216.3	NP_004421.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EGR3	ENST00000317216.3 link	c.360C>A	p.Leu120Leu	synonymous_variant	Exon 2 of 2	1	NM_004430.3	ENSP00000318057.2

Frequencies

GnomAD3 genomes

AF:

0.0849

AC:

12915

AN:

152106

Hom.:

578

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0821

Gnomad AMI

AF:

0.00439

Gnomad AMR

AF:

0.103

Gnomad ASJ

AF:

0.0409

Gnomad EAS

AF:

0.206

Gnomad SAS

AF:

0.0819

Gnomad FIN

AF:

0.0849

Gnomad MID

AF:

0.0696

Gnomad NFE

AF:

0.0766

Gnomad OTH

AF:

0.0919

GnomAD2 exomes

AF:

0.0961

AC:

24012

AN:

249842

AF XY:

0.0917

show subpopulations

Gnomad AFR exome

AF:

0.0831

Gnomad AMR exome

AF:

0.152

Gnomad ASJ exome

AF:

0.0499

Gnomad EAS exome

AF:

0.199

Gnomad FIN exome

AF:

0.0814

Gnomad NFE exome

AF:

0.0770

Gnomad OTH exome

AF:

0.0860

GnomAD4 exome

AF:

0.0824

AC:

120486

AN:

1461674

Hom.:

5700

Cov.:

AF XY:

0.0817

AC XY:

59414

AN XY:

727128

show subpopulations

African (AFR)

AF:

0.0849

AC:

2841

AN:

33480

American (AMR)

AF:

0.146

AC:

6538

AN:

44710

Ashkenazi Jewish (ASJ)

AF:

0.0481

AC:

1256

AN:

26134

East Asian (EAS)

AF:

0.230

AC:

9118

AN:

39700

South Asian (SAS)

AF:

0.0759

AC:

6550

AN:

86258

European-Finnish (FIN)

AF:

0.0865

AC:

4605

AN:

53240

Middle Eastern (MID)

AF:

0.0531

AC:

306

AN:

5768

European-Non Finnish (NFE)

AF:

0.0759

AC:

84437

AN:

1111996

Other (OTH)

AF:

0.0801

AC:

4835

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

7912

15824

23736

31648

39560

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3264

6528

9792

13056

16320

<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:

0.0849

AC:

12923

AN:

152224

Hom.:

578

Cov.:

AF XY:

0.0853

AC XY:

6353

AN XY:

74438

show subpopulations

African (AFR)

AF:

0.0821

AC:

3413

AN:

41550

American (AMR)

AF:

0.104

AC:

1586

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.0409

AC:

142

AN:

3470

East Asian (EAS)

AF:

0.206

AC:

1063

AN:

5168

South Asian (SAS)

AF:

0.0818

AC:

395

AN:

4830

European-Finnish (FIN)

AF:

0.0849

AC:

900

AN:

10606

Middle Eastern (MID)

AF:

0.0714

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0766

AC:

5206

AN:

67980

Other (OTH)

AF:

0.0914

AC:

193

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

619

1238

1856

2475

3094

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

154

308

462

616

770

<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:

0.0797

Hom.:

524

Bravo

AF:

0.0893

Asia WGS

AF:

0.143

AC:

498

AN:

3478

EpiCase

AF:

0.0759

EpiControl

AF:

0.0730

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Sep 14, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.65

CADD

Benign

(source)

DANN

Benign

0.92

PhyloP100

3.8

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over