rs10197559

Variant names:

• chr2-215321102-C-T
• rs10197559
• NM_004044.7:c.290+1371C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_004044.7(ATIC):​c.290+1371C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.211 in 152,126 control chromosomes in the GnomAD database, including 4,299 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.21 (4299 hom., cov: 32)
• Consequence: ATIC NM_004044.7 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.401
• Publications: 7 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 2-215321102-C-T is Benign according to our data. Variant chr2-215321102-C-T is described in ClinVar as [Benign]. Clinvar id is 1545064.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.297 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATIC	NM_004044.7	c.290+1371C>T		intron_variant	Intron 4 of 15	ENST00000236959.14	NP_004035.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATIC	ENST00000236959.14	c.290+1371C>T		intron_variant	Intron 4 of 15	1	NM_004044.7	ENSP00000236959.9

Frequencies

GnomAD3 genomes AF: 0.211 AC: 32062 AN: 152008 Hom.: 4300 Cov.: 32

Gnomad AFR AF: 0.0857

Gnomad AMI AF: 0.365

Gnomad AMR AF: 0.183

Gnomad ASJ AF: 0.202

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.0594

Gnomad FIN AF: 0.329

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.300

Gnomad OTH AF: 0.213

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

GnomAD4 genome AF: 0.211 AC: 32056 AN: 152126 Hom.: 4299 Cov.: 32 AF XY: 0.207 AC XY: 15398 AN XY: 74356

African (AFR) AF: 0.0856 AC: 3553 AN: 41522

American (AMR) AF: 0.183 AC: 2796 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.202 AC: 702 AN: 3472

East Asian (EAS) AF: 0.00154 AC: 8 AN: 5182

South Asian (SAS) AF: 0.0597 AC: 288 AN: 4828

European-Finnish (FIN) AF: 0.329 AC: 3477 AN: 10568

Middle Eastern (MID) AF: 0.177 AC: 52 AN: 294

European-Non Finnish (NFE) AF: 0.300 AC: 20402 AN: 67964

Other (OTH) AF: 0.211 AC: 446 AN: 2114

Alfa AF: 0.265 Hom.: 17811

Bravo AF: 0.196

Asia WGS AF: 0.0330 AC: 117 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.14
DANN	Benign	0.88
PhyloP100		-0.40
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
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: rs10197559; hg19: chr2-216185825;