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: 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=-0.96).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.21 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.1320+642C>T		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.1320+642C>T	intron	N/A	ENSP00000236959.9	P31939-1
ATIC	ENST00000435675.5	TSL:2	c.1317+642C>T	intron	N/A	ENSP00000415935.1	P31939-2
ATIC	ENST00000957330.1		c.1320+642C>T	intron	N/A	ENSP00000627389.1

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 v4.9

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over