chr2-215325297-C-G

Variant names:

Variant summary

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

The NM_004044.7(ATIC):c.347C>G(p.Thr116Ser) variant causes a missense change. The variant allele was found at a frequency of 0.319 in 1,610,906 control chromosomes in the GnomAD database, including 86,062 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.26 ( 6016 hom., cov: 32)

Exomes 𝑓: 0.33 ( 80046 hom. )

Consequence

ATIC
NM_004044.7 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 6.03

Publications

126 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0017181039).

BP6

Variant 2-215325297-C-G is Benign according to our data. Variant chr2-215325297-C-G is described in ClinVar as [Benign]. Clinvar id is 801893.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.456 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATIC	NM_004044.7 link	c.347C>G	p.Thr116Ser	missense_variant	Exon 5 of 16	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.347C>G	p.Thr116Ser	missense_variant	Exon 5 of 16	1	NM_004044.7	ENSP00000236959.9		P31939-1

Frequencies

GnomAD3 genomes

AF:

0.259

AC:

39259

AN:

151858

Hom.:

6007

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0915

Gnomad AMI

AF:

0.415

Gnomad AMR

AF:

0.300

Gnomad ASJ

AF:

0.349

Gnomad EAS

AF:

0.272

Gnomad SAS

AF:

0.470

Gnomad FIN

AF:

0.271

Gnomad MID

AF:

0.329

Gnomad NFE

AF:

0.325

Gnomad OTH

AF:

0.278

GnomAD2 exomes

AF:

0.325

AC:

81828

AN:

251410

AF XY:

0.338

show subpopulations

Gnomad AFR exome

AF:

0.0877

Gnomad AMR exome

AF:

0.334

Gnomad ASJ exome

AF:

0.349

Gnomad EAS exome

AF:

0.294

Gnomad FIN exome

AF:

0.277

Gnomad NFE exome

AF:

0.329

Gnomad OTH exome

AF:

0.318

GnomAD4 exome

AF:

0.325

AC:

474575

AN:

1458932

Hom.:

80046

Cov.:

AF XY:

0.331

AC XY:

240355

AN XY:

725936

show subpopulations

African (AFR)

AF:

0.0778

AC:

2602

AN:

33458

American (AMR)

AF:

0.328

AC:

14672

AN:

44710

Ashkenazi Jewish (ASJ)

AF:

0.345

AC:

9010

AN:

26098

East Asian (EAS)

AF:

0.249

AC:

9885

AN:

39662

South Asian (SAS)

AF:

0.473

AC:

40780

AN:

86174

European-Finnish (FIN)

AF:

0.277

AC:

14792

AN:

53388

Middle Eastern (MID)

AF:

0.335

AC:

1931

AN:

5764

European-Non Finnish (NFE)

AF:

0.326

AC:

361190

AN:

1109396

Other (OTH)

AF:

0.327

AC:

19713

AN:

60282

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.460

Heterozygous variant carriers

14229

28458

42688

56917

71146

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.259

AC:

39289

AN:

151974

Hom.:

6016

Cov.:

AF XY:

0.259

AC XY:

19235

AN XY:

74282

show subpopulations

African (AFR)

AF:

0.0917

AC:

3803

AN:

41492

American (AMR)

AF:

0.301

AC:

4587

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.349

AC:

1211

AN:

3468

East Asian (EAS)

AF:

0.272

AC:

1405

AN:

5168

South Asian (SAS)

AF:

0.472

AC:

2273

AN:

4818

European-Finnish (FIN)

AF:

0.271

AC:

2841

AN:

10492

Middle Eastern (MID)

AF:

0.313

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.325

AC:

22105

AN:

67958

Other (OTH)

AF:

0.281

AC:

594

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1416

2831

4247

5662

7078

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.313

Hom.:

2565

Bravo

AF:

0.253

TwinsUK

AF:

0.325

AC:

1205

ALSPAC

AF:

0.328

AC:

1263

ESP6500AA

AF:

0.0962

AC:

424

ESP6500EA

AF:

0.324

AC:

2786

ExAC

AF:

0.323

AC:

39268

Asia WGS

AF:

0.388

AC:

1346

AN:

3478

EpiCase

AF:

0.338

EpiControl

AF:

0.334

ClinVar

Significance: Benign

Submissions summary: Benign:5

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

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

AICA-ribosiduria

Benign:2

Jul 14, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

May 28, 2019

Mendelics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

ATIC-related disorder

Benign:1

Oct 18, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.085

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.16

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.50

D;.;.

Eigen

Benign

0.028

Eigen_PC

Benign

0.20

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.57

T;T;T

MetaRNN

Benign

0.0017

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.1

L;.;.

PhyloP100

6.0

PrimateAI

Benign

0.47

PROVEAN

Uncertain

-2.6

D;D;D

REVEL

Uncertain

0.32

Sift

Benign

0.13

T;T;T

Sift4G

Benign

0.33

T;T;T

Polyphen

0.0010

B;.;.

Vest4

0.11

MutPred

0.24

Gain of disorder (P = 0.0286);.;.;

MPC

0.050

ClinPred

0.033

GERP RS

5.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.51

gMVP

0.53

Mutation Taster

=86/14

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

Splicevardb

2.0

SpliceAI score (max)

0.040

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

chr2-215325297-C-G

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