rs4672768

chr2-215349401-G-Achr2-215349401-G-Cchr2-215349401-G-T

Variant summary

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

The NM_004044.7(ATIC):c.1660-135G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.319 in 1,570,326 control chromosomes in the GnomAD database, including 83,737 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 0.26 (5998 hom., cov: 32)
  • Exomes 𝑓: 0.33 (77739 hom.)
• Consequence: ATIC NM_004044.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.415

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=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.454 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATIC	NM_004044.7	c.1660-135G>A		intron_variant		ENST00000236959.14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATIC	ENST00000236959.14	c.1660-135G>A		intron_variant		1	NM_004044.7	P1

Frequencies

GnomAD3 genomes AF: 0.257 AC: 39138 AN: 152044 Hom.: 5989 Cov.: 32

Gnomad AFR AF: 0.0890

Gnomad AMI AF: 0.385

Gnomad AMR AF: 0.300

Gnomad ASJ AF: 0.350

Gnomad EAS AF: 0.278

Gnomad SAS AF: 0.469

Gnomad FIN AF: 0.270

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.325

Gnomad OTH AF: 0.277

GnomAD4 exome AF: 0.326 AC: 461873 AN: 1418164 Hom.: 77739 Cov.: 27 AF XY: 0.331 AC XY: 233876 AN XY: 705636

Gnomad4 AFR exome AF: 0.0756

Gnomad4 AMR exome AF: 0.324

Gnomad4 ASJ exome AF: 0.346

Gnomad4 EAS exome AF: 0.253

Gnomad4 SAS exome AF: 0.474

Gnomad4 FIN exome AF: 0.276

Gnomad4 NFE exome AF: 0.326

Gnomad4 OTH exome AF: 0.327

GnomAD4 genome AF: 0.257 AC: 39169 AN: 152162 Hom.: 5998 Cov.: 32 AF XY: 0.258 AC XY: 19179 AN XY: 74388

Gnomad4 AFR AF: 0.0892

Gnomad4 AMR AF: 0.300

Gnomad4 ASJ AF: 0.350

Gnomad4 EAS AF: 0.279

Gnomad4 SAS AF: 0.470

Gnomad4 FIN AF: 0.270

Gnomad4 NFE AF: 0.325

Gnomad4 OTH AF: 0.280

Alfa AF: 0.299 Hom.: 3391

Bravo AF: 0.251

Asia WGS AF: 0.390 AC: 1353 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	0.97
Dann	Benign	0.17

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: rs4672768; hg19: chr2-216214124;