NM_004044.7:c.1228-1578C>G

Variant names:

• chr2-215343201-C-G
• rs13002052
• NM_004044.7:c.1228-1578C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004044.7(ATIC):​c.1228-1578C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.237 in 151,074 control chromosomes in the GnomAD database, including 5,099 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 0.24 (5099 hom., cov: 31)
• Consequence: ATIC NM_004044.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.105
• Publications: 5 publications found

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.433 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.1228-1578C>G		intron	N/A	NP_004035.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATIC	ENST00000236959.14	TSL:1 MANE Select	c.1228-1578C>G		intron	N/A	ENSP00000236959.9
	ATIC	ENST00000435675.5	TSL:2	c.1225-1578C>G		intron	N/A	ENSP00000415935.1
	ATIC	ENST00000957330.1		c.1228-1578C>G		intron	N/A	ENSP00000627389.1

Frequencies

GnomAD3 genomes AF: 0.237 AC: 35748 AN: 150960 Hom.: 5091 Cov.: 31

Gnomad AFR AF: 0.0722

Gnomad AMI AF: 0.302

Gnomad AMR AF: 0.282

Gnomad ASJ AF: 0.319

Gnomad EAS AF: 0.277

Gnomad SAS AF: 0.448

Gnomad FIN AF: 0.262

Gnomad MID AF: 0.309

Gnomad NFE AF: 0.299

Gnomad OTH AF: 0.251

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.237 AC: 35775 AN: 151074 Hom.: 5099 Cov.: 31 AF XY: 0.238 AC XY: 17532 AN XY: 73774

African (AFR) AF: 0.0723 AC: 2970 AN: 41072

American (AMR) AF: 0.282 AC: 4281 AN: 15188

Ashkenazi Jewish (ASJ) AF: 0.319 AC: 1103 AN: 3462

East Asian (EAS) AF: 0.277 AC: 1423 AN: 5138

South Asian (SAS) AF: 0.449 AC: 2155 AN: 4798

European-Finnish (FIN) AF: 0.262 AC: 2700 AN: 10290

Middle Eastern (MID) AF: 0.288 AC: 84 AN: 292

European-Non Finnish (NFE) AF: 0.299 AC: 20251 AN: 67824

Other (OTH) AF: 0.254 AC: 535 AN: 2106

Alfa AF: 0.256 Hom.: 689

Bravo AF: 0.229

Asia WGS AF: 0.380 AC: 1320 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.3
DANN	Benign	0.63
PhyloP100		-0.10
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs13002052; hg19: chr2-216207924;