Genetic Variant ATIC:c.380-56C>T (chr2-215325931-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_004044.7(ATIC):c.380-56C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.454 in 1,580,358 control chromosomes in the GnomAD database, including 165,880 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 0.46 ( 16533 hom., cov: 32)

Exomes 𝑓: 0.45 ( 149347 hom. )

Consequence

ATIC
NM_004044.7 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.467

Publications

28 publications found

Variant links:

Genes affected

ATIC (HGNC:794): (5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/IMP cyclohydrolase) This gene encodes a bifunctional protein that catalyzes the last two steps of the de novo purine biosynthetic pathway. The N-terminal domain has phosphoribosylaminoimidazolecarboxamide formyltransferase activity, and the C-terminal domain has IMP cyclohydrolase activity. A mutation in this gene results in AICA-ribosiduria. [provided by RefSeq, Sep 2009]

ATIC Gene-Disease associations (from GenCC):

AICA-ribosiduria
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Orphanet

ATIC 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=-0.87).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.502 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATIC	NM_004044.7 link	c.380-56C>T		intron_variant	Intron 5 of 15	ENST00000236959.14	NP_004035.2	P31939-1V9HWH7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATIC	ENST00000236959.14 link	c.380-56C>T		intron_variant	Intron 5 of 15	1	NM_004044.7	ENSP00000236959.9		P31939-1

Frequencies

GnomAD3 genomes

AF:

0.462

AC:

70133

AN:

151914

Hom.:

16523

Cov.:

show subpopulations

Gnomad AFR

AF:

0.508

Gnomad AMI

AF:

0.461

Gnomad AMR

AF:

0.418

Gnomad ASJ

AF:

0.411

Gnomad EAS

AF:

0.222

Gnomad SAS

AF:

0.323

Gnomad FIN

AF:

0.491

Gnomad MID

AF:

0.427

Gnomad NFE

AF:

0.470

Gnomad OTH

AF:

0.459

GnomAD4 exome

AF:

0.453

AC:

647664

AN:

1428326

Hom.:

149347

AF XY:

0.449

AC XY:

319744

AN XY:

712386

show subpopulations

African (AFR)

AF:

0.517

AC:

16859

AN:

32608

American (AMR)

AF:

0.358

AC:

15857

AN:

44346

Ashkenazi Jewish (ASJ)

AF:

0.414

AC:

10707

AN:

25854

East Asian (EAS)

AF:

0.274

AC:

10783

AN:

39304

South Asian (SAS)

AF:

0.313

AC:

26629

AN:

85092

European-Finnish (FIN)

AF:

0.481

AC:

25459

AN:

52918

Middle Eastern (MID)

AF:

0.425

AC:

2423

AN:

5704

European-Non Finnish (NFE)

AF:

0.474

AC:

513391

AN:

1083308

Other (OTH)

AF:

0.432

AC:

25556

AN:

59192

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

17664

35329

52993

70658

88322

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

15038

30076

45114

60152

75190

<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:

0.462

AC:

70164

AN:

152032

Hom.:

16533

Cov.:

AF XY:

0.459

AC XY:

34097

AN XY:

74314

show subpopulations

African (AFR)

AF:

0.508

AC:

21040

AN:

41440

American (AMR)

AF:

0.418

AC:

6383

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.411

AC:

1425

AN:

3470

East Asian (EAS)

AF:

0.222

AC:

1146

AN:

5166

South Asian (SAS)

AF:

0.321

AC:

1549

AN:

4820

European-Finnish (FIN)

AF:

0.491

AC:

5189

AN:

10564

Middle Eastern (MID)

AF:

0.439

AC:

129

AN:

294

European-Non Finnish (NFE)

AF:

0.470

AC:

31926

AN:

67976

Other (OTH)

AF:

0.455

AC:

960

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1959

3918

5877

7836

9795

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

636

1272

1908

2544

3180

<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:

0.463

Hom.:

11770

Bravo

AF:

0.457

Asia WGS

AF:

0.278

AC:

970

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.39

(source)

DANN

Benign

0.63

PhyloP100

-0.47

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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