2-215325122-A-G

Position:

• chr2-215325122-A-G

Variant summary

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

The NM_004044.7(ATIC):​c.291-119A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.224 in 764,356 control chromosomes in the GnomAD database, including 21,233 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 0.20 (3517 hom., cov: 33)
  • Exomes 𝑓: 0.23 (17716 hom.)
• Consequence: ATIC NM_004044.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.68

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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.488 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATIC	NM_004044.7	c.291-119A>G		intron_variant		ENST00000236959.14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATIC	ENST00000236959.14	c.291-119A>G		intron_variant		1	NM_004044.7	P1

Frequencies

GnomAD3 genomes AF: 0.204 AC: 31040 AN: 151924 Hom.: 3512 Cov.: 33

Gnomad AFR AF: 0.140

Gnomad AMI AF: 0.123

Gnomad AMR AF: 0.253

Gnomad ASJ AF: 0.240

Gnomad EAS AF: 0.504

Gnomad SAS AF: 0.206

Gnomad FIN AF: 0.237

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.204

Gnomad OTH AF: 0.211

GnomAD4 exome AF: 0.229 AC: 140211 AN: 612314 Hom.: 17716 AF XY: 0.227 AC XY: 75383 AN XY: 331844

Gnomad4 AFR exome AF: 0.139

Gnomad4 AMR exome AF: 0.307

Gnomad4 ASJ exome AF: 0.244

Gnomad4 EAS exome AF: 0.478

Gnomad4 SAS exome AF: 0.215

Gnomad4 FIN exome AF: 0.243

Gnomad4 NFE exome AF: 0.201

Gnomad4 OTH exome AF: 0.228

GnomAD4 genome AF: 0.204 AC: 31083 AN: 152042 Hom.: 3517 Cov.: 33 AF XY: 0.209 AC XY: 15495 AN XY: 74288

Gnomad4 AFR AF: 0.140

Gnomad4 AMR AF: 0.253

Gnomad4 ASJ AF: 0.240

Gnomad4 EAS AF: 0.504

Gnomad4 SAS AF: 0.206

Gnomad4 FIN AF: 0.237

Gnomad4 NFE AF: 0.204

Gnomad4 OTH AF: 0.214

Alfa AF: 0.203 Hom.: 1569

Bravo AF: 0.204

Asia WGS AF: 0.314 AC: 1091 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.030
DANN	Benign	0.32

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: rs3772078; hg19: chr2-216189845;