dbSNP rs3772078: ATIC:c.291-119A>G (chr2-215325122-A-G) – 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.291-119A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.224 in 764,356 control chromosomes in the GnomAD database, including 21,233 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 0.20 ( 3517 hom., cov: 33)

Exomes 𝑓: 0.23 ( 17716 hom. )

Consequence

ATIC
NM_004044.7 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.68

Publications

11 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: G2P, Orphanet, Labcorp Genetics (formerly Invitae)

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=-0.85).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.488 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004044.7. 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
	ATIC	NM_004044.7	MANE Select	c.291-119A>G		intron	N/A	NP_004035.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ATIC	ENST00000236959.14	TSL:1 MANE Select	c.291-119A>G	intron	N/A	ENSP00000236959.9	P31939-1
ATIC	ENST00000435675.5	TSL:2	c.288-119A>G	intron	N/A	ENSP00000415935.1	P31939-2
ATIC	ENST00000957330.1		c.291-119A>G	intron	N/A	ENSP00000627389.1

Frequencies

GnomAD3 genomes

AF:

0.204

AC:

31040

AN:

151924

Hom.:

3512

Cov.:

show subpopulations

Gnomad AFR

AF:

0.140

Gnomad AMI

AF:

0.123

Gnomad AMR

AF:

0.253

Gnomad ASJ

AF:

0.240

Gnomad EAS

AF:

0.504

Gnomad SAS

AF:

0.206

Gnomad FIN

AF:

0.237

Gnomad MID

AF:

0.222

Gnomad NFE

AF:

0.204

Gnomad OTH

AF:

0.211

GnomAD4 exome

AF:

0.229

AC:

140211

AN:

612314

Hom.:

17716

AF XY:

0.227

AC XY:

75383

AN XY:

331844

show subpopulations

African (AFR)

AF:

0.139

AC:

2314

AN:

16608

American (AMR)

AF:

0.307

AC:

11268

AN:

36696

Ashkenazi Jewish (ASJ)

AF:

0.244

AC:

4678

AN:

19198

East Asian (EAS)

AF:

0.478

AC:

16558

AN:

34668

South Asian (SAS)

AF:

0.215

AC:

13792

AN:

64038

European-Finnish (FIN)

AF:

0.243

AC:

11368

AN:

46750

Middle Eastern (MID)

AF:

0.230

AC:

704

AN:

3060

European-Non Finnish (NFE)

AF:

0.201

AC:

72325

AN:

359678

Other (OTH)

AF:

0.228

AC:

7204

AN:

31618

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.519

Heterozygous variant carriers

4907

9814

14720

19627

24534

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

890

1780

2670

3560

4450

<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:

0.204

AC:

31083

AN:

152042

Hom.:

3517

Cov.:

AF XY:

0.209

AC XY:

15495

AN XY:

74288

show subpopulations

African (AFR)

AF:

0.140

AC:

5810

AN:

41490

American (AMR)

AF:

0.253

AC:

3868

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.240

AC:

833

AN:

3470

East Asian (EAS)

AF:

0.504

AC:

2592

AN:

5140

South Asian (SAS)

AF:

0.206

AC:

991

AN:

4822

European-Finnish (FIN)

AF:

0.237

AC:

2497

AN:

10552

Middle Eastern (MID)

AF:

0.224

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.204

AC:

13863

AN:

67982

Other (OTH)

AF:

0.214

AC:

451

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1272

2544

3815

5087

6359

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

342

684

1026

1368

1710

<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:

0.202

Hom.:

1721

Bravo

AF:

0.204

Asia WGS

AF:

0.314

AC:

1091

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.030

(source)

DANN

Benign

0.32

PhyloP100

-2.7

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over