2-215340444-G-A

Variant names:

• chr2-215340444-G-A
• rs16853826
• NM_004044.7:c.1227+1537G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_004044.7(ATIC):​c.1227+1537G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.155 in 152,126 control chromosomes in the GnomAD database, including 2,145 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.16 (2145 hom., cov: 32)
• Consequence: ATIC NM_004044.7 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.209
• Publications: 15 publications found

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]

ATIC Gene-Disease associations (from GenCC):

• AICA-ribosiduria

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Orphanet

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 2-215340444-G-A is Benign according to our data. Variant chr2-215340444-G-A is described in ClinVar as Benign. ClinVar VariationId is 1545046.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.481 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004044.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATIC	NM_004044.7	MANE Select	c.1227+1537G>A		intron	N/A	NP_004035.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATIC	ENST00000236959.14	TSL:1 MANE Select	c.1227+1537G>A		intron	N/A	ENSP00000236959.9
	ATIC	ENST00000435675.5	TSL:2	c.1224+1537G>A		intron	N/A	ENSP00000415935.1
	ATIC	ENST00000426233.1	TSL:2	c.231+1537G>A		intron	N/A	ENSP00000401936.1

Frequencies

GnomAD3 genomes AF: 0.155 AC: 23560 AN: 152006 Hom.: 2140 Cov.: 32

Gnomad AFR AF: 0.151

Gnomad AMI AF: 0.0844

Gnomad AMR AF: 0.193

Gnomad ASJ AF: 0.0934

Gnomad EAS AF: 0.497

Gnomad SAS AF: 0.140

Gnomad FIN AF: 0.118

Gnomad MID AF: 0.134

Gnomad NFE AF: 0.134

Gnomad OTH AF: 0.145

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.155 AC: 23587 AN: 152126 Hom.: 2145 Cov.: 32 AF XY: 0.156 AC XY: 11602 AN XY: 74374

African (AFR) AF: 0.151 AC: 6276 AN: 41484

American (AMR) AF: 0.193 AC: 2952 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0934 AC: 324 AN: 3470

East Asian (EAS) AF: 0.497 AC: 2564 AN: 5154

South Asian (SAS) AF: 0.139 AC: 671 AN: 4826

European-Finnish (FIN) AF: 0.118 AC: 1250 AN: 10600

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.134 AC: 9120 AN: 67994

Other (OTH) AF: 0.148 AC: 313 AN: 2110

Alfa AF: 0.146 Hom.: 2896

Bravo AF: 0.162

Asia WGS AF: 0.281 AC: 976 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jan 28, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.0
DANN	Benign	0.64
PhyloP100		-0.21
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs16853826; hg19: chr2-216205167;