dbSNP rs3743476: AEN:p.Glu58Glu (chr15-88626383-A-G) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_022767.4(AEN):c.174A>G(p.Glu58Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.324 in 1,611,358 control chromosomes in the GnomAD database, including 89,739 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 ( 6747 hom., cov: 34)

Exomes 𝑓: 0.33 ( 82992 hom. )

Consequence

AEN
NM_022767.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0150

Publications

14 publications found

Variant links:

Genes affected

AEN (HGNC:25722): (apoptosis enhancing nuclease) Enables exonuclease activity. Involved in intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator and response to ionizing radiation. Located in nuclear membrane; nucleolus; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

AEN links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP7

Synonymous conserved (PhyloP=0.015 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.351 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AEN	NM_022767.4 link	c.174A>G	p.Glu58Glu	synonymous_variant	Exon 2 of 4	ENST00000332810.4	NP_073604.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AEN	ENST00000332810.4 link	c.174A>G	p.Glu58Glu	synonymous_variant	Exon 2 of 4	1	NM_022767.4	ENSP00000331944.3

Frequencies

GnomAD3 genomes

AF:

0.271

AC:

41171

AN:

152072

Hom.:

6748

Cov.:

show subpopulations

Gnomad AFR

AF:

0.105

Gnomad AMI

AF:

0.436

Gnomad AMR

AF:

0.239

Gnomad ASJ

AF:

0.309

Gnomad EAS

AF:

0.179

Gnomad SAS

AF:

0.212

Gnomad FIN

AF:

0.469

Gnomad MID

AF:

0.298

Gnomad NFE

AF:

0.355

Gnomad OTH

AF:

0.283

GnomAD2 exomes

AF:

0.283

AC:

69161

AN:

244174

AF XY:

0.290

show subpopulations

Gnomad AFR exome

AF:

0.100

Gnomad AMR exome

AF:

0.170

Gnomad ASJ exome

AF:

0.303

Gnomad EAS exome

AF:

0.157

Gnomad FIN exome

AF:

0.446

Gnomad NFE exome

AF:

0.352

Gnomad OTH exome

AF:

0.303

GnomAD4 exome

AF:

0.329

AC:

480373

AN:

1459168

Hom.:

82992

Cov.:

AF XY:

0.327

AC XY:

237334

AN XY:

725666

show subpopulations

African (AFR)

AF:

0.101

AC:

3384

AN:

33464

American (AMR)

AF:

0.174

AC:

7714

AN:

44454

Ashkenazi Jewish (ASJ)

AF:

0.308

AC:

8031

AN:

26096

East Asian (EAS)

AF:

0.206

AC:

8172

AN:

39656

South Asian (SAS)

AF:

0.215

AC:

18548

AN:

86090

European-Finnish (FIN)

AF:

0.443

AC:

23334

AN:

52632

Middle Eastern (MID)

AF:

0.301

AC:

1724

AN:

5720

European-Non Finnish (NFE)

AF:

0.352

AC:

391230

AN:

1110792

Other (OTH)

AF:

0.303

AC:

18236

AN:

60264

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

22055

44110

66164

88219

110274

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12166

24332

36498

48664

60830

<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:

0.271

AC:

41175

AN:

152190

Hom.:

6747

Cov.:

AF XY:

0.273

AC XY:

20322

AN XY:

74400

show subpopulations

African (AFR)

AF:

0.105

AC:

4352

AN:

41572

American (AMR)

AF:

0.238

AC:

3642

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.309

AC:

1073

AN:

3472

East Asian (EAS)

AF:

0.179

AC:

921

AN:

5158

South Asian (SAS)

AF:

0.214

AC:

1033

AN:

4824

European-Finnish (FIN)

AF:

0.469

AC:

4966

AN:

10586

Middle Eastern (MID)

AF:

0.293

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.355

AC:

24112

AN:

67970

Other (OTH)

AF:

0.281

AC:

594

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1495

2991

4486

5982

7477

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

416

832

1248

1664

2080

<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:

0.315

Hom.:

3788

Bravo

AF:

0.246

Asia WGS

AF:

0.173

AC:

604

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

6.8

(source)

DANN

Benign

0.35

PhyloP100

0.015

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