rs7586969

Variant names:

• chr2-215342502-G-A
• rs7586969
• NM_004044.7:c.1228-2277G>A

Your query was ambiguous. Multiple possible variants found:

• chr2-215342502-G-A
• chr2-215342502-G-C
• chr2-215342502-G-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.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
• 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: G2P, Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATIC	NM_004044.7	MANE Select	c.1228-2277G>A		intron	N/A	NP_004035.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATIC	ENST00000236959.14	TSL:1 MANE Select	c.1228-2277G>A		intron	N/A	ENSP00000236959.9	P31939-1
	ATIC	ENST00000435675.5	TSL:2	c.1225-2277G>A		intron	N/A	ENSP00000415935.1	P31939-2
	ATIC	ENST00000957330.1		c.1228-2277G>A		intron	N/A	ENSP00000627389.1

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

African (AFR) AF: 0.358 AC: 14848 AN: 41424

American (AMR) AF: 0.685 AC: 10456 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.629 AC: 2178 AN: 3464

East Asian (EAS) AF: 0.997 AC: 5156 AN: 5174

South Asian (SAS) AF: 0.833 AC: 4016 AN: 4822

European-Finnish (FIN) AF: 0.546 AC: 5765 AN: 10566

Middle Eastern (MID) AF: 0.646 AC: 190 AN: 294

European-Non Finnish (NFE) AF: 0.621 AC: 42172 AN: 67946

Other (OTH) AF: 0.596 AC: 1257 AN: 2110

Alfa AF: 0.610 Hom.: 37359

Bravo AF: 0.572

Asia WGS AF: 0.880 AC: 3057 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.30
DANN	Benign	0.31
PhyloP100		-2.0
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: rs7586969; hg19: chr2-216207225;