chr2-215312084-T-G

Position:

• chr2-215312084-T-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_004044.7(ATIC):​c.-59T>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.295 in 1,528,280 control chromosomes in the GnomAD database, including 70,884 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.23 (5130 hom., cov: 34)
  • Exomes 𝑓: 0.30 (65754 hom.)
• Consequence: ATIC NM_004044.7 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.144

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 2-215312084-T-G is Benign according to our data. Variant chr2-215312084-T-G is described in ClinVar as [Benign]. Clinvar id is 1192366.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.439 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATIC	NM_004044.7	c.-59T>G		5_prime_UTR_variant	1/16	ENST00000236959.14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATIC	ENST00000236959.14	c.-59T>G		5_prime_UTR_variant	1/16	1	NM_004044.7	P1

Frequencies

GnomAD3 genomes AF: 0.233 AC: 35377 AN: 152100 Hom.: 5126 Cov.: 34

Gnomad AFR AF: 0.0559

Gnomad AMI AF: 0.327

Gnomad AMR AF: 0.282

Gnomad ASJ AF: 0.319

Gnomad EAS AF: 0.220

Gnomad SAS AF: 0.454

Gnomad FIN AF: 0.270

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.302

Gnomad OTH AF: 0.248

GnomAD4 exome AF: 0.302 AC: 415869 AN: 1376064 Hom.: 65754 Cov.: 33 AF XY: 0.308 AC XY: 209190 AN XY: 679094

Gnomad4 AFR exome AF: 0.0447

Gnomad4 AMR exome AF: 0.304

Gnomad4 ASJ exome AF: 0.312

Gnomad4 EAS exome AF: 0.172

Gnomad4 SAS exome AF: 0.459

Gnomad4 FIN exome AF: 0.277

Gnomad4 NFE exome AF: 0.303

Gnomad4 OTH exome AF: 0.305

GnomAD4 genome AF: 0.233 AC: 35393 AN: 152216 Hom.: 5130 Cov.: 34 AF XY: 0.235 AC XY: 17469 AN XY: 74440

Gnomad4 AFR AF: 0.0557

Gnomad4 AMR AF: 0.282

Gnomad4 ASJ AF: 0.319

Gnomad4 EAS AF: 0.220

Gnomad4 SAS AF: 0.455

Gnomad4 FIN AF: 0.270

Gnomad4 NFE AF: 0.302

Gnomad4 OTH AF: 0.252

Alfa AF: 0.145 Hom.: 295

Bravo AF: 0.224

Asia WGS AF: 0.368 AC: 1278 AN: 3474

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

AICA-ribosiduria Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	4.9
DANN	Benign	0.58

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: rs4535042; hg19: chr2-216176807;