2-215345513-C-T

Position:

• chr2-215345513-C-T

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.62

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=-0.96).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.21 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATIC	NM_004044.7	c.1320+642C>T		intron_variant		ENST00000236959.14	NP_004035.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATIC	ENST00000236959.14	c.1320+642C>T		intron_variant		1	NM_004044.7	ENSP00000236959	P1

Frequencies

GnomAD3 genomes AF: 0.133 AC: 20170 AN: 152024 Hom.: 1710 Cov.: 33

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.: 62 Cov.: 0 AF XY: 0.164 AC XY: 403 AN XY: 2462

Gnomad4 AFR exome AF: 0.111

Gnomad4 AMR exome AF: 0.188

Gnomad4 ASJ exome AF: 0.0714

Gnomad4 EAS exome AF: 0.250

Gnomad4 SAS exome AF: 0.201

Gnomad4 FIN exome AF: 0.150

Gnomad4 NFE exome AF: 0.138

Gnomad4 OTH exome AF: 0.180

GnomAD4 genome AF: 0.132 AC: 20159 AN: 152144 Hom.: 1708 Cov.: 33 AF XY: 0.137 AC XY: 10160 AN XY: 74370

Gnomad4 AFR AF: 0.0338

Gnomad4 AMR AF: 0.183

Gnomad4 ASJ AF: 0.186

Gnomad4 EAS AF: 0.220

Gnomad4 SAS AF: 0.221

Gnomad4 FIN AF: 0.157

Gnomad4 NFE AF: 0.161

Gnomad4 OTH AF: 0.149

Alfa AF: 0.161 Hom.: 4226

Bravo AF: 0.130

Asia WGS AF: 0.201 AC: 700 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.0030
DANN	Benign	0.48

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: rs16853834; hg19: chr2-216210236;