dbSNP rs35201266: EGR3:c.154+607G>A (chr8-22692184-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_004430.3(EGR3):c.154+607G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.283 in 1,387,582 control chromosomes in the GnomAD database, including 57,221 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 0.27 ( 5947 hom., cov: 33)

Exomes 𝑓: 0.28 ( 51274 hom. )

Consequence

EGR3
NM_004430.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.392

Publications

9 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:

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=-0.89).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.41 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EGR3	NM_004430.3 link	c.154+607G>A		intron_variant	Intron 1 of 1	ENST00000317216.3	NP_004421.2	Q06889-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EGR3	ENST00000317216.3 link	c.154+607G>A		intron_variant	Intron 1 of 1	1	NM_004430.3	ENSP00000318057.2		Q06889-1

Frequencies

GnomAD3 genomes

AF:

0.270

AC:

40986

AN:

152042

Hom.:

5942

Cov.:

show subpopulations

Gnomad AFR

AF:

0.172

Gnomad AMI

AF:

0.309

Gnomad AMR

AF:

0.418

Gnomad ASJ

AF:

0.376

Gnomad EAS

AF:

0.277

Gnomad SAS

AF:

0.269

Gnomad FIN

AF:

0.268

Gnomad MID

AF:

0.370

Gnomad NFE

AF:

0.288

Gnomad OTH

AF:

0.313

GnomAD4 exome

AF:

0.285

AC:

351831

AN:

1235422

Hom.:

51274

Cov.:

AF XY:

0.285

AC XY:

170921

AN XY:

598882

show subpopulations

African (AFR)

AF:

0.174

AC:

4246

AN:

24466

American (AMR)

AF:

0.498

AC:

7390

AN:

14848

Ashkenazi Jewish (ASJ)

AF:

0.365

AC:

6510

AN:

17814

East Asian (EAS)

AF:

0.317

AC:

8984

AN:

28324

South Asian (SAS)

AF:

0.282

AC:

16553

AN:

58732

European-Finnish (FIN)

AF:

0.269

AC:

7862

AN:

29194

Middle Eastern (MID)

AF:

0.359

AC:

1377

AN:

3832

European-Non Finnish (NFE)

AF:

0.282

AC:

284204

AN:

1007396

Other (OTH)

AF:

0.289

AC:

14705

AN:

50816

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

14381

28761

43142

57522

71903

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10112

20224

30336

40448

50560

<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:

0.270

AC:

41016

AN:

152160

Hom.:

5947

Cov.:

AF XY:

0.271

AC XY:

20180

AN XY:

74388

show subpopulations

African (AFR)

AF:

0.173

AC:

7175

AN:

41548

American (AMR)

AF:

0.418

AC:

6395

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.376

AC:

1304

AN:

3472

East Asian (EAS)

AF:

0.276

AC:

1424

AN:

5156

South Asian (SAS)

AF:

0.268

AC:

1292

AN:

4828

European-Finnish (FIN)

AF:

0.268

AC:

2841

AN:

10602

Middle Eastern (MID)

AF:

0.361

AC:

106

AN:

294

European-Non Finnish (NFE)

AF:

0.288

AC:

19540

AN:

67940

Other (OTH)

AF:

0.311

AC:

657

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1566

3132

4697

6263

7829

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

428

856

1284

1712

2140

<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:

0.271

Hom.:

738

Bravo

AF:

0.277

Asia WGS

AF:

0.266

AC:

924

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

7.2

(source)

DANN

Benign

0.91

PhyloP100

0.39

PromoterAI

-0.038

Neutral

(source)

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