rs3772078

Variant names:

• chr2-215325122-A-G
• rs3772078
• NM_004044.7:c.291-119A>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.291-119A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.224 in 764,356 control chromosomes in the GnomAD database, including 21,233 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 0.20 (3517 hom., cov: 33)
  • Exomes 𝑓: 0.23 (17716 hom.)
• Consequence: ATIC NM_004044.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.68
• Publications: 11 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 = 0.488 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATIC	NM_004044.7	MANE Select	c.291-119A>G		intron	N/A	NP_004035.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATIC	ENST00000236959.14	TSL:1 MANE Select	c.291-119A>G		intron	N/A	ENSP00000236959.9
	ATIC	ENST00000435675.5	TSL:2	c.288-119A>G		intron	N/A	ENSP00000415935.1
	ATIC	ENST00000413174.1	TSL:5	c.114-119A>G		intron	N/A	ENSP00000402393.1

Frequencies

GnomAD3 genomes AF: 0.204 AC: 31040 AN: 151924 Hom.: 3512 Cov.: 33

Gnomad AFR AF: 0.140

Gnomad AMI AF: 0.123

Gnomad AMR AF: 0.253

Gnomad ASJ AF: 0.240

Gnomad EAS AF: 0.504

Gnomad SAS AF: 0.206

Gnomad FIN AF: 0.237

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.204

Gnomad OTH AF: 0.211

GnomAD4 exome AF: 0.229 AC: 140211 AN: 612314 Hom.: 17716 AF XY: 0.227 AC XY: 75383 AN XY: 331844

African (AFR) AF: 0.139 AC: 2314 AN: 16608

American (AMR) AF: 0.307 AC: 11268 AN: 36696

Ashkenazi Jewish (ASJ) AF: 0.244 AC: 4678 AN: 19198

East Asian (EAS) AF: 0.478 AC: 16558 AN: 34668

South Asian (SAS) AF: 0.215 AC: 13792 AN: 64038

European-Finnish (FIN) AF: 0.243 AC: 11368 AN: 46750

Middle Eastern (MID) AF: 0.230 AC: 704 AN: 3060

European-Non Finnish (NFE) AF: 0.201 AC: 72325 AN: 359678

Other (OTH) AF: 0.228 AC: 7204 AN: 31618

GnomAD4 genome AF: 0.204 AC: 31083 AN: 152042 Hom.: 3517 Cov.: 33 AF XY: 0.209 AC XY: 15495 AN XY: 74288

African (AFR) AF: 0.140 AC: 5810 AN: 41490

American (AMR) AF: 0.253 AC: 3868 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.240 AC: 833 AN: 3470

East Asian (EAS) AF: 0.504 AC: 2592 AN: 5140

South Asian (SAS) AF: 0.206 AC: 991 AN: 4822

European-Finnish (FIN) AF: 0.237 AC: 2497 AN: 10552

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

European-Non Finnish (NFE) AF: 0.204 AC: 13863 AN: 67982

Other (OTH) AF: 0.214 AC: 451 AN: 2110

Alfa AF: 0.202 Hom.: 1721

Bravo AF: 0.204

Asia WGS AF: 0.314 AC: 1091 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.030
DANN	Benign	0.32
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: rs3772078; hg19: chr2-216189845;