Genetic Variant AIM2:p.Glu83Glu (chr1-159073251-C-T) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_004833.3(AIM2):c.249G>A(p.Glu83Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00439 in 1,614,094 control chromosomes in the GnomAD database, including 199 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.018 ( 101 hom., cov: 33)

Exomes 𝑓: 0.0030 ( 98 hom. )

Consequence

AIM2
NM_004833.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -3.03

Publications

2 publications found

Variant links:

Genes affected

AIM2 (HGNC:357): (absent in melanoma 2) AIM2 is a member of the IFI20X /IFI16 family. It plays a putative role in tumorigenic reversion and may control cell proliferation. Interferon-gamma induces expression of AIM2. [provided by RefSeq, Jul 2008]

AIM2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 1-159073251-C-T is Benign according to our data. Variant chr1-159073251-C-T is described in ClinVar as Benign. ClinVar VariationId is 775617.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-3.03 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0578 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004833.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AIM2	NM_004833.3	MANE Select	c.249G>A	p.Glu83Glu	synonymous	Exon 2 of 6	NP_004824.1	O14862
	AIM2	NM_001348247.2		c.-54+3382G>A		intron	N/A	NP_001335176.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
AIM2	ENST00000368130.9	TSL:1 MANE Select	c.249G>A	p.Glu83Glu	synonymous	Exon 2 of 6	ENSP00000357112.4	O14862
AIM2	ENST00000411768.2	TSL:5	c.249G>A	p.Glu83Glu	synonymous	Exon 5 of 9	ENSP00000512039.1	O14862
AIM2	ENST00000695580.1		c.249G>A	p.Glu83Glu	synonymous	Exon 3 of 7	ENSP00000512040.1	O14862

Frequencies

GnomAD3 genomes

AF:

0.0179

AC:

2730

AN:

152152

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0593

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00700

Gnomad ASJ

AF:

0.00547

Gnomad EAS

AF:

0.000577

Gnomad SAS

AF:

0.00518

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.00107

Gnomad OTH

AF:

0.0181

GnomAD2 exomes

AF:

0.00583

AC:

1465

AN:

251168

AF XY:

0.00504

show subpopulations

Gnomad AFR exome

AF:

0.0585

Gnomad AMR exome

AF:

0.00414

Gnomad ASJ exome

AF:

0.00407

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.00122

Gnomad OTH exome

AF:

0.00669

GnomAD4 exome

AF:

0.00296

AC:

4321

AN:

1461824

Hom.:

Cov.:

AF XY:

0.00291

AC XY:

2117

AN XY:

727204

show subpopulations

African (AFR)

AF:

0.0594

AC:

1987

AN:

33478

American (AMR)

AF:

0.00494

AC:

221

AN:

44712

Ashkenazi Jewish (ASJ)

AF:

0.00360

AC:

AN:

26134

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39700

South Asian (SAS)

AF:

0.00499

AC:

430

AN:

86258

European-Finnish (FIN)

AF:

0.000112

AC:

AN:

53408

Middle Eastern (MID)

AF:

0.0454

AC:

262

AN:

5768

European-Non Finnish (NFE)

AF:

0.000788

AC:

876

AN:

1111970

Other (OTH)

AF:

0.00735

AC:

444

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

239

478

718

957

1196

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

188

282

376

470

<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:

0.0181

AC:

2759

AN:

152270

Hom.:

101

Cov.:

AF XY:

0.0175

AC XY:

1306

AN XY:

74452

show subpopulations

African (AFR)

AF:

0.0598

AC:

2483

AN:

41530

American (AMR)

AF:

0.00699

AC:

107

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00547

AC:

AN:

3472

East Asian (EAS)

AF:

0.000578

AC:

AN:

5186

South Asian (SAS)

AF:

0.00498

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.000188

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.0340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00107

AC:

AN:

68016

Other (OTH)

AF:

0.0180

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

125

250

376

501

626

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

150

<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:

0.00837

Hom.:

Bravo

AF:

0.0207

Asia WGS

AF:

0.00895

AC:

AN:

3478

EpiCase

AF:

0.00125

EpiControl

AF:

0.00113

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

0.45

(source)

DANN

Benign

0.48

PhyloP100

-3.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over