Genetic Variant ATIC:c.815-102T>C (chr2-215333248-T-C) – 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.815-102T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.543 in 922,674 control chromosomes in the GnomAD database, including 140,036 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 0.48 ( 18784 hom., cov: 33)

Exomes 𝑓: 0.56 ( 121252 hom. )

Consequence

ATIC
NM_004044.7 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.503

Publications

29 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=-0.81).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.756 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATIC	NM_004044.7 link	c.815-102T>C		intron_variant	Intron 8 of 15	ENST00000236959.14	NP_004035.2	P31939-1V9HWH7

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
ATIC	ENST00000236959.14 link	c.815-102T>C	intron_variant	Intron 8 of 15	1	NM_004044.7	ENSP00000236959.9	P31939-1
ATIC	ENST00000435675.5 link	c.812-102T>C	intron_variant	Intron 7 of 14	2		ENSP00000415935.1	P31939-2
ATIC	ENST00000427397.5 link	n.*708-102T>C	intron_variant	Intron 7 of 8	5		ENSP00000394317.1	F2Z3E8
ATIC	ENST00000443953.5 link	n.*912-102T>C	intron_variant	Intron 8 of 15	2		ENSP00000406792.1	F2Z3E8

Frequencies

GnomAD3 genomes

AF:

0.478

AC:

72620

AN:

151842

Hom.:

18749

Cov.:

show subpopulations

Gnomad AFR

AF:

0.286

Gnomad AMI

AF:

0.519

Gnomad AMR

AF:

0.559

Gnomad ASJ

AF:

0.589

Gnomad EAS

AF:

0.776

Gnomad SAS

AF:

0.669

Gnomad FIN

AF:

0.509

Gnomad MID

AF:

0.557

Gnomad NFE

AF:

0.529

Gnomad OTH

AF:

0.498

GnomAD4 exome

AF:

0.556

AC:

428382

AN:

770712

Hom.:

121252

AF XY:

0.562

AC XY:

229063

AN XY:

407458

show subpopulations

African (AFR)

AF:

0.283

AC:

5546

AN:

19616

American (AMR)

AF:

0.628

AC:

24072

AN:

38334

Ashkenazi Jewish (ASJ)

AF:

0.587

AC:

12448

AN:

21206

East Asian (EAS)

AF:

0.719

AC:

25501

AN:

35472

South Asian (SAS)

AF:

0.679

AC:

47144

AN:

69394

European-Finnish (FIN)

AF:

0.520

AC:

26564

AN:

51124

Middle Eastern (MID)

AF:

0.565

AC:

2091

AN:

3700

European-Non Finnish (NFE)

AF:

0.534

AC:

264236

AN:

494440

Other (OTH)

AF:

0.555

AC:

20780

AN:

37426

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

8992

17984

26977

35969

44961

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4430

8860

13290

17720

22150

<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:

0.478

AC:

72701

AN:

151962

Hom.:

18784

Cov.:

AF XY:

0.482

AC XY:

35817

AN XY:

74294

show subpopulations

African (AFR)

AF:

0.286

AC:

11841

AN:

41382

American (AMR)

AF:

0.560

AC:

8546

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.589

AC:

2042

AN:

3464

East Asian (EAS)

AF:

0.776

AC:

4017

AN:

5176

South Asian (SAS)

AF:

0.671

AC:

3235

AN:

4822

European-Finnish (FIN)

AF:

0.509

AC:

5370

AN:

10560

Middle Eastern (MID)

AF:

0.548

AC:

161

AN:

294

European-Non Finnish (NFE)

AF:

0.529

AC:

35957

AN:

67974

Other (OTH)

AF:

0.503

AC:

1059

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1866

3732

5598

7464

9330

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

670

1340

2010

2680

3350

<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:

0.521

Hom.:

86659

Bravo

AF:

0.473

Asia WGS

AF:

0.702

AC:

2438

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.53

(source)

DANN

Benign

0.73

PhyloP100

-0.50

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