rs1880586

Variant names:

• chr2-215330448-G-A
• rs1880586
• NM_004044.7:c.689-1934G>A

Your query was ambiguous. Multiple possible variants found:

• chr2-215330448-G-A
• chr2-215330448-G-C

Variant summary

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

The NM_004044.7(ATIC):​c.689-1934G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.52 in 151,906 control chromosomes in the GnomAD database, including 21,059 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 0.52 (21059 hom., cov: 32)
• Consequence: ATIC NM_004044.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.70
• Publications: 9 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=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.757 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.689-1934G>A		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.689-1934G>A		intron	N/A	ENSP00000236959.9	P31939-1
	ATIC	ENST00000435675.5	TSL:2	c.686-1934G>A		intron	N/A	ENSP00000415935.1	P31939-2
	ATIC	ENST00000957330.1		c.689-1934G>A		intron	N/A	ENSP00000627389.1

Frequencies

GnomAD3 genomes AF: 0.520 AC: 78918 AN: 151788 Hom.: 21025 Cov.: 32

Gnomad AFR AF: 0.429

Gnomad AMI AF: 0.537

Gnomad AMR AF: 0.576

Gnomad ASJ AF: 0.590

Gnomad EAS AF: 0.776

Gnomad SAS AF: 0.670

Gnomad FIN AF: 0.509

Gnomad MID AF: 0.570

Gnomad NFE AF: 0.530

Gnomad OTH AF: 0.531

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

GnomAD4 genome AF: 0.520 AC: 78998 AN: 151906 Hom.: 21059 Cov.: 32 AF XY: 0.523 AC XY: 38836 AN XY: 74214

African (AFR) AF: 0.429 AC: 17765 AN: 41404

American (AMR) AF: 0.576 AC: 8800 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.590 AC: 2046 AN: 3468

East Asian (EAS) AF: 0.777 AC: 4008 AN: 5160

South Asian (SAS) AF: 0.672 AC: 3241 AN: 4824

European-Finnish (FIN) AF: 0.509 AC: 5355 AN: 10520

Middle Eastern (MID) AF: 0.558 AC: 164 AN: 294

European-Non Finnish (NFE) AF: 0.530 AC: 36001 AN: 67948

Other (OTH) AF: 0.536 AC: 1128 AN: 2106

Alfa AF: 0.525 Hom.: 3986

Bravo AF: 0.521

Asia WGS AF: 0.712 AC: 2474 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.13
DANN	Benign	0.51
PhyloP100		-2.7
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: rs1880586; hg19: chr2-216195171;