rs3821353

Variant names:

• chr2-215333056-G-T
• rs3821353
• NM_004044.7:c.815-294G>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.815-294G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.209 in 151,982 control chromosomes in the GnomAD database, including 3,608 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 0.21 (3608 hom., cov: 31)
• Consequence: ATIC NM_004044.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.380
• Publications: 18 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.483 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATIC	NM_004044.7	c.815-294G>T		intron_variant	Intron 8 of 15	ENST00000236959.14	NP_004035.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATIC	ENST00000236959.14	c.815-294G>T		intron_variant	Intron 8 of 15	1	NM_004044.7	ENSP00000236959.9
ATIC	ENST00000435675.5	c.812-294G>T		intron_variant	Intron 7 of 14	2		ENSP00000415935.1
ATIC	ENST00000427397.5	n.*708-294G>T		intron_variant	Intron 7 of 8	5		ENSP00000394317.1
ATIC	ENST00000443953.5	n.*912-294G>T		intron_variant	Intron 8 of 15	2		ENSP00000406792.1

Frequencies

GnomAD3 genomes AF: 0.209 AC: 31700 AN: 151864 Hom.: 3600 Cov.: 31

Gnomad AFR AF: 0.156

Gnomad AMI AF: 0.129

Gnomad AMR AF: 0.254

Gnomad ASJ AF: 0.240

Gnomad EAS AF: 0.498

Gnomad SAS AF: 0.205

Gnomad FIN AF: 0.238

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.204

Gnomad OTH AF: 0.211

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

GnomAD4 genome AF: 0.209 AC: 31748 AN: 151982 Hom.: 3608 Cov.: 31 AF XY: 0.213 AC XY: 15795 AN XY: 74248

African (AFR) AF: 0.156 AC: 6475 AN: 41442

American (AMR) AF: 0.254 AC: 3875 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.240 AC: 834 AN: 3470

East Asian (EAS) AF: 0.499 AC: 2569 AN: 5152

South Asian (SAS) AF: 0.205 AC: 986 AN: 4812

European-Finnish (FIN) AF: 0.238 AC: 2512 AN: 10552

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.204 AC: 13864 AN: 67986

Other (OTH) AF: 0.213 AC: 450 AN: 2110

Alfa AF: 0.209 Hom.: 8114

Bravo AF: 0.209

Asia WGS AF: 0.314 AC: 1091 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.5
DANN	Benign	0.50
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: rs3821353; hg19: chr2-216197779;