dbSNP rs4672768: ATIC:c.1660-135G>A (chr2-215349401-G-A) – 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.1660-135G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.319 in 1,570,326 control chromosomes in the GnomAD database, including 83,737 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 0.26 ( 5998 hom., cov: 32)

Exomes 𝑓: 0.33 ( 77739 hom. )

Consequence

ATIC
NM_004044.7 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.415

Publications

13 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=-0.84).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.454 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATIC	NM_004044.7 link	c.1660-135G>A		intron_variant	Intron 15 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.1660-135G>A		intron_variant	Intron 15 of 15	1	NM_004044.7	ENSP00000236959.9		P31939-1

Frequencies

GnomAD3 genomes

AF:

0.257

AC:

39138

AN:

152044

Hom.:

5989

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0890

Gnomad AMI

AF:

0.385

Gnomad AMR

AF:

0.300

Gnomad ASJ

AF:

0.350

Gnomad EAS

AF:

0.278

Gnomad SAS

AF:

0.469

Gnomad FIN

AF:

0.270

Gnomad MID

AF:

0.329

Gnomad NFE

AF:

0.325

Gnomad OTH

AF:

0.277

GnomAD4 exome

AF:

0.326

AC:

461873

AN:

1418164

Hom.:

77739

Cov.:

AF XY:

0.331

AC XY:

233876

AN XY:

705636

show subpopulations

African (AFR)

AF:

0.0756

AC:

2458

AN:

32512

American (AMR)

AF:

0.324

AC:

13295

AN:

41050

Ashkenazi Jewish (ASJ)

AF:

0.346

AC:

8911

AN:

25782

East Asian (EAS)

AF:

0.253

AC:

9831

AN:

38892

South Asian (SAS)

AF:

0.474

AC:

39586

AN:

83572

European-Finnish (FIN)

AF:

0.276

AC:

13302

AN:

48190

Middle Eastern (MID)

AF:

0.335

AC:

1856

AN:

5542

European-Non Finnish (NFE)

AF:

0.326

AC:

353316

AN:

1083632

Other (OTH)

AF:

0.327

AC:

19318

AN:

58992

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.515

Heterozygous variant carriers

17132

34265

51397

68530

85662

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11380

22760

34140

45520

56900

<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:

0.257

AC:

39169

AN:

152162

Hom.:

5998

Cov.:

AF XY:

0.258

AC XY:

19179

AN XY:

74388

show subpopulations

African (AFR)

AF:

0.0892

AC:

3705

AN:

41542

American (AMR)

AF:

0.300

AC:

4582

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.350

AC:

1213

AN:

3470

East Asian (EAS)

AF:

0.279

AC:

1439

AN:

5164

South Asian (SAS)

AF:

0.470

AC:

2265

AN:

4816

European-Finnish (FIN)

AF:

0.270

AC:

2860

AN:

10586

Middle Eastern (MID)

AF:

0.313

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.325

AC:

22071

AN:

67986

Other (OTH)

AF:

0.280

AC:

592

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

1459

2919

4378

5838

7297

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

424

848

1272

1696

2120

<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:

0.300

Hom.:

3799

Bravo

AF:

0.251

Asia WGS

AF:

0.390

AC:

1353

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

0.97

(source)

DANN

Benign

0.17

PhyloP100

-0.41

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