rs1983462

Variant names:

• chr2-215330558-G-A
• rs1983462
• NM_004044.7:c.689-1824G>A

Variant summary

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

The NM_004044.7(ATIC):​c.689-1824G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.306 in 151,892 control chromosomes in the GnomAD database, including 7,694 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 0.31 (7694 hom., cov: 31)
• Consequence: ATIC NM_004044.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.78
• 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: Labcorp Genetics (formerly Invitae), G2P, Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.389 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATIC	NM_004044.7	c.689-1824G>A		intron_variant	Intron 7 of 15	ENST00000236959.14	NP_004035.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATIC	ENST00000236959.14	c.689-1824G>A		intron_variant	Intron 7 of 15	1	NM_004044.7	ENSP00000236959.9
ATIC	ENST00000435675.5	c.686-1824G>A		intron_variant	Intron 6 of 14	2		ENSP00000415935.1
ATIC	ENST00000427397.5	n.*582-1824G>A		intron_variant	Intron 6 of 8	5		ENSP00000394317.1
ATIC	ENST00000443953.5	n.*786-1824G>A		intron_variant	Intron 7 of 15	2		ENSP00000406792.1

Frequencies

GnomAD3 genomes AF: 0.306 AC: 46406 AN: 151774 Hom.: 7684 Cov.: 31

Gnomad AFR AF: 0.394

Gnomad AMI AF: 0.374

Gnomad AMR AF: 0.225

Gnomad ASJ AF: 0.211

Gnomad EAS AF: 0.00212

Gnomad SAS AF: 0.103

Gnomad FIN AF: 0.332

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.308

Gnomad OTH AF: 0.291

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

GnomAD4 genome AF: 0.306 AC: 46442 AN: 151892 Hom.: 7694 Cov.: 31 AF XY: 0.300 AC XY: 22263 AN XY: 74236

African (AFR) AF: 0.394 AC: 16329 AN: 41408

American (AMR) AF: 0.225 AC: 3428 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.211 AC: 733 AN: 3466

East Asian (EAS) AF: 0.00212 AC: 11 AN: 5186

South Asian (SAS) AF: 0.103 AC: 495 AN: 4806

European-Finnish (FIN) AF: 0.332 AC: 3496 AN: 10520

Middle Eastern (MID) AF: 0.235 AC: 69 AN: 294

European-Non Finnish (NFE) AF: 0.308 AC: 20934 AN: 67940

Other (OTH) AF: 0.289 AC: 607 AN: 2100

Alfa AF: 0.299 Hom.: 9097

Bravo AF: 0.302

Asia WGS AF: 0.0740 AC: 261 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.054
DANN	Benign	0.68
PhyloP100		-2.8
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: rs1983462; hg19: chr2-216195281;