rs4673990

Variant names:

• chr2-215341330-A-G
• rs4673990
• NM_004044.7:c.1227+2423A>G

Variant summary

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

The NM_004044.7(ATIC):​c.1227+2423A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.413 in 152,018 control chromosomes in the GnomAD database, including 14,273 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 0.41 (14273 hom., cov: 32)
• Consequence: ATIC NM_004044.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.08
• Publications: 24 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.756 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.1227+2423A>G		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.1227+2423A>G		intron	N/A	ENSP00000236959.9	P31939-1
	ATIC	ENST00000435675.5	TSL:2	c.1224+2423A>G		intron	N/A	ENSP00000415935.1	P31939-2
	ATIC	ENST00000957330.1		c.1227+2423A>G		intron	N/A	ENSP00000627389.1

Frequencies

GnomAD3 genomes AF: 0.413 AC: 62759 AN: 151898 Hom.: 14251 Cov.: 32

Gnomad AFR AF: 0.241

Gnomad AMI AF: 0.470

Gnomad AMR AF: 0.493

Gnomad ASJ AF: 0.443

Gnomad EAS AF: 0.775

Gnomad SAS AF: 0.613

Gnomad FIN AF: 0.389

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.459

Gnomad OTH AF: 0.422

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

GnomAD4 genome AF: 0.413 AC: 62816 AN: 152018 Hom.: 14273 Cov.: 32 AF XY: 0.415 AC XY: 30800 AN XY: 74272

African (AFR) AF: 0.241 AC: 10007 AN: 41468

American (AMR) AF: 0.494 AC: 7545 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.443 AC: 1537 AN: 3472

East Asian (EAS) AF: 0.776 AC: 4008 AN: 5166

South Asian (SAS) AF: 0.614 AC: 2955 AN: 4814

European-Finnish (FIN) AF: 0.389 AC: 4097 AN: 10538

Middle Eastern (MID) AF: 0.449 AC: 132 AN: 294

European-Non Finnish (NFE) AF: 0.459 AC: 31200 AN: 67962

Other (OTH) AF: 0.429 AC: 906 AN: 2114

Alfa AF: 0.447 Hom.: 9773

Bravo AF: 0.413

Asia WGS AF: 0.671 AC: 2329 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.2
DANN	Benign	0.84
PhyloP100		-1.1
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)		0.0		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: rs4673990; hg19: chr2-216206053;