rs7586969

Positions:

• chr2-215342502-G-A
• chr2-215342502-G-C
• chr2-215342502-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.1228-2277G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.57 in 151,980 control chromosomes in the GnomAD database, including 26,444 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 0.57 (26444 hom., cov: 32)
• Consequence: ATIC NM_004044.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.03

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.974 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATIC	NM_004044.7	c.1228-2277G>A		intron_variant		ENST00000236959.14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATIC	ENST00000236959.14	c.1228-2277G>A		intron_variant		1	NM_004044.7	P1

Frequencies

GnomAD3 genomes AF: 0.570 AC: 86529 AN: 151862 Hom.: 26429 Cov.: 32

Gnomad AFR AF: 0.359

Gnomad AMI AF: 0.589

Gnomad AMR AF: 0.684

Gnomad ASJ AF: 0.629

Gnomad EAS AF: 0.997

Gnomad SAS AF: 0.833

Gnomad FIN AF: 0.546

Gnomad MID AF: 0.658

Gnomad NFE AF: 0.621

Gnomad OTH AF: 0.591

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

GnomAD4 genome AF: 0.570 AC: 86573 AN: 151980 Hom.: 26444 Cov.: 32 AF XY: 0.575 AC XY: 42750 AN XY: 74296

Gnomad4 AFR AF: 0.358

Gnomad4 AMR AF: 0.685

Gnomad4 ASJ AF: 0.629

Gnomad4 EAS AF: 0.997

Gnomad4 SAS AF: 0.833

Gnomad4 FIN AF: 0.546

Gnomad4 NFE AF: 0.621

Gnomad4 OTH AF: 0.596

Alfa AF: 0.616 Hom.: 29023

Bravo AF: 0.572

Asia WGS AF: 0.880 AC: 3057 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	0.30
DANN	Benign	0.31

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: rs7586969; hg19: chr2-216207225;