Genetic Variant NM_004044.7: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.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATIC	NM_004044.7	MANE Select	c.815-102T>C		intron	N/A	NP_004035.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
ATIC	ENST00000236959.14	TSL:1 MANE Select	c.815-102T>C	intron	N/A	ENSP00000236959.9
ATIC	ENST00000435675.5	TSL:2	c.812-102T>C	intron	N/A	ENSP00000415935.1
ATIC	ENST00000427397.5	TSL:5	n.*708-102T>C	intron	N/A	ENSP00000394317.1

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 v4.9

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over