chr2-215331322-G-T

Variant names:

• chr2-215331322-G-T
• rs13005416
• NM_004044.7:c.689-1060G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004044.7(ATIC):​c.689-1060G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.484 in 150,510 control chromosomes in the GnomAD database, including 18,903 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 0.48 (18903 hom., cov: 29)
• Consequence: ATIC NM_004044.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.376
• Publications: 7 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: G2P, Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.761 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATIC	NM_004044.7	MANE Select	c.689-1060G>T		intron	N/A	NP_004035.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATIC	ENST00000236959.14	TSL:1 MANE Select	c.689-1060G>T		intron	N/A	ENSP00000236959.9	P31939-1
	ATIC	ENST00000435675.5	TSL:2	c.686-1060G>T		intron	N/A	ENSP00000415935.1	P31939-2
	ATIC	ENST00000957330.1		c.689-1060G>T		intron	N/A	ENSP00000627389.1

Frequencies

GnomAD3 genomes AF: 0.484 AC: 72740 AN: 150412 Hom.: 18873 Cov.: 29

Gnomad AFR AF: 0.300

Gnomad AMI AF: 0.534

Gnomad AMR AF: 0.561

Gnomad ASJ AF: 0.590

Gnomad EAS AF: 0.780

Gnomad SAS AF: 0.672

Gnomad FIN AF: 0.509

Gnomad MID AF: 0.565

Gnomad NFE AF: 0.530

Gnomad OTH AF: 0.504

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

GnomAD4 genome AF: 0.484 AC: 72813 AN: 150510 Hom.: 18903 Cov.: 29 AF XY: 0.487 AC XY: 35706 AN XY: 73322

African (AFR) AF: 0.301 AC: 12323 AN: 40962

American (AMR) AF: 0.561 AC: 8471 AN: 15092

Ashkenazi Jewish (ASJ) AF: 0.590 AC: 2046 AN: 3466

East Asian (EAS) AF: 0.781 AC: 3988 AN: 5108

South Asian (SAS) AF: 0.674 AC: 3223 AN: 4784

European-Finnish (FIN) AF: 0.509 AC: 5100 AN: 10026

Middle Eastern (MID) AF: 0.556 AC: 159 AN: 286

European-Non Finnish (NFE) AF: 0.530 AC: 35958 AN: 67798

Other (OTH) AF: 0.510 AC: 1062 AN: 2084

Alfa AF: 0.513 Hom.: 9762

Bravo AF: 0.479

Asia WGS AF: 0.702 AC: 2436 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.8
DANN	Benign	0.64
PhyloP100		-0.38
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs13005416; hg19: chr2-216196045;