rs13002052

Positions:

• chr2-215343201-C-G
• chr2-215343201-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000236959.14(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 ENST00000236959.14 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.105

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATIC	NM_004044.7	c.1228-1578C>G		intron_variant		ENST00000236959.14	NP_004035.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATIC	ENST00000236959.14	c.1228-1578C>G		intron_variant		1	NM_004044.7	ENSP00000236959	P1

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

Gnomad4 AFR AF: 0.0723

Gnomad4 AMR AF: 0.282

Gnomad4 ASJ AF: 0.319

Gnomad4 EAS AF: 0.277

Gnomad4 SAS AF: 0.449

Gnomad4 FIN AF: 0.262

Gnomad4 NFE AF: 0.299

Gnomad4 OTH AF: 0.254

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.3
DANN	Benign	0.63

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

LitVar

Other links and lift over

dbSNP: rs13002052; hg19: chr2-216207924;