dbSNP rs16853834: ATIC:c.1320+642C>T (chr2-215345513-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.1320+642C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.133 in 156,746 control chromosomes in the GnomAD database, including 1,770 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 0.13 ( 1708 hom., cov: 33)

Exomes 𝑓: 0.16 ( 62 hom. )

Consequence

ATIC
NM_004044.7 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.62

Publications

26 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=-0.96).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.21 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATIC	NM_004044.7 link	c.1320+642C>T		intron_variant	Intron 13 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.1320+642C>T		intron_variant	Intron 13 of 15	1	NM_004044.7	ENSP00000236959.9		P31939-1

Frequencies

GnomAD3 genomes

AF:

0.133

AC:

20170

AN:

152024

Hom.:

1710

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0339

Gnomad AMI

AF:

0.116

Gnomad AMR

AF:

0.183

Gnomad ASJ

AF:

0.186

Gnomad EAS

AF:

0.220

Gnomad SAS

AF:

0.223

Gnomad FIN

AF:

0.157

Gnomad MID

AF:

0.190

Gnomad NFE

AF:

0.161

Gnomad OTH

AF:

0.151

GnomAD4 exome

AF:

0.159

AC:

730

AN:

4602

Hom.:

Cov.:

AF XY:

0.164

AC XY:

403

AN XY:

2462

show subpopulations

African (AFR)

AF:

0.111

AC:

AN:

American (AMR)

AF:

0.188

AC:

203

AN:

1080

Ashkenazi Jewish (ASJ)

AF:

0.0714

AC:

AN:

East Asian (EAS)

AF:

0.250

AC:

AN:

100

South Asian (SAS)

AF:

0.201

AC:

AN:

412

European-Finnish (FIN)

AF:

0.150

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.138

AC:

383

AN:

2784

Other (OTH)

AF:

0.180

AC:

AN:

150

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.521

Heterozygous variant carriers

128

160

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.132

AC:

20159

AN:

152144

Hom.:

1708

Cov.:

AF XY:

0.137

AC XY:

10160

AN XY:

74370

show subpopulations

African (AFR)

AF:

0.0338

AC:

1405

AN:

41536

American (AMR)

AF:

0.183

AC:

2794

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.186

AC:

646

AN:

3470

East Asian (EAS)

AF:

0.220

AC:

1136

AN:

5172

South Asian (SAS)

AF:

0.221

AC:

1064

AN:

4804

European-Finnish (FIN)

AF:

0.157

AC:

1664

AN:

10568

Middle Eastern (MID)

AF:

0.197

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.161

AC:

10972

AN:

67992

Other (OTH)

AF:

0.149

AC:

314

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

889

1779

2668

3558

4447

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

222

444

666

888

1110

<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:

0.155

Hom.:

8776

Bravo

AF:

0.130

Asia WGS

AF:

0.201

AC:

700

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

0.0030

(source)

DANN

Benign

0.48

PhyloP100

-3.6

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