rs3821353

Positions:

• chr2-215333056-G-T

Variant summary

Our verdict is Benign. Variant got -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

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
ATIC	NM_004044.7	c.815-294G>T		intron_variant		ENST00000236959.14	NP_004035.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATIC	ENST00000236959.14	c.815-294G>T		intron_variant		1	NM_004044.7	ENSP00000236959.9
ATIC	ENST00000435675.5	c.812-294G>T		intron_variant		2		ENSP00000415935.1
ATIC	ENST00000427397.5	n.*708-294G>T		intron_variant		5		ENSP00000394317.1
ATIC	ENST00000443953.5	n.*912-294G>T		intron_variant		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

Gnomad4 AFR AF: 0.156

Gnomad4 AMR AF: 0.254

Gnomad4 ASJ AF: 0.240

Gnomad4 EAS AF: 0.499

Gnomad4 SAS AF: 0.205

Gnomad4 FIN AF: 0.238

Gnomad4 NFE AF: 0.204

Gnomad4 OTH AF: 0.213

Alfa AF: 0.207 Hom.: 1661

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs3821353; hg19: chr2-216197779;