Variant chr2-215347616-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_StrongBA1

The NM_004044.7(ATIC):c.1503+675T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.32 in 490,610 control chromosomes in the GnomAD database, including 27,164 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as drug response (★★★).

Frequency

Genomes: 𝑓 0.27 ( 6101 hom., cov: 31)

Exomes 𝑓: 0.34 ( 21063 hom. )

Consequence

ATIC
NM_004044.7 intron

Scores

Splicing: ADA: 0.00003789

Clinical Significance

drug response reviewed by expert panel B:1O:1

Conservation

PhyloP100: -0.622

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 2-215347616-T-C is Benign according to our data. Variant chr2-215347616-T-C is described in ClinVar as [drug_response]. Clinvar id is 225999.Status of the report is reviewed_by_expert_panel, 3 stars. We mark this variant Likely_benign, oryginal submissions are: {Benign=1, drug_response=1}.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.454 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATIC	NM_004044.7 link	c.1503+675T>C		intron_variant	Intron 14 of 15	ENST00000236959.14	NP_004035.2	P31939-1V9HWH7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATIC	ENST00000236959.14 link	c.1503+675T>C		intron_variant	Intron 14 of 15	1	NM_004044.7	ENSP00000236959.9		P31939-1

Frequencies

GnomAD3 genomes

AF:

0.266

AC:

40398

AN:

151642

Hom.:

6092

Cov.:

show subpopulations

Gnomad AFR

AF:

0.121

Gnomad AMI

AF:

0.389

Gnomad AMR

AF:

0.303

Gnomad ASJ

AF:

0.349

Gnomad EAS

AF:

0.276

Gnomad SAS

AF:

0.469

Gnomad FIN

AF:

0.268

Gnomad MID

AF:

0.334

Gnomad NFE

AF:

0.325

Gnomad OTH

AF:

0.282

GnomAD3 exomes

AF:

0.340

AC:

47119

AN:

138606

Hom.:

8478

AF XY:

0.353

AC XY:

26451

AN XY:

74924

show subpopulations

Gnomad AFR exome

AF:

0.118

Gnomad AMR exome

AF:

0.330

Gnomad ASJ exome

AF:

0.346

Gnomad EAS exome

AF:

0.307

Gnomad SAS exome

AF:

0.479

Gnomad FIN exome

AF:

0.274

Gnomad NFE exome

AF:

0.329

Gnomad OTH exome

AF:

0.327

GnomAD4 exome

AF:

0.343

AC:

116330

AN:

338850

Hom.:

21063

Cov.:

AF XY:

0.357

AC XY:

67511

AN XY:

189216

show subpopulations

Gnomad4 AFR exome

AF:

0.119

Gnomad4 AMR exome

AF:

0.329

Gnomad4 ASJ exome

AF:

0.341

Gnomad4 EAS exome

AF:

0.257

Gnomad4 SAS exome

AF:

0.473

Gnomad4 FIN exome

AF:

0.275

Gnomad4 NFE exome

AF:

0.329

Gnomad4 OTH exome

AF:

0.322

GnomAD4 genome

AF:

0.266

AC:

40429

AN:

151760

Hom.:

6101

Cov.:

AF XY:

0.266

AC XY:

19740

AN XY:

74138

show subpopulations

Gnomad4 AFR

AF:

0.121

Gnomad4 AMR

AF:

0.303

Gnomad4 ASJ

AF:

0.349

Gnomad4 EAS

AF:

0.276

Gnomad4 SAS

AF:

0.470

Gnomad4 FIN

AF:

0.268

Gnomad4 NFE

AF:

0.325

Gnomad4 OTH

AF:

0.284

Alfa

AF:

0.324

Hom.:

4788

Bravo

AF:

0.263

Asia WGS

AF:

0.391

AC:

1358

AN:

3478

ClinVar

Significance: drug response

Submissions summary: Benign:1Other:1

Revision: reviewed by expert panel

LINK: link

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

- -

methotrexate response - Efficacy

Other:1

Mar 24, 2021

PharmGKB

Significance: drug response

Review Status: reviewed by expert panel

Collection Method: curation

PharmGKB Level of Evidence 2B: Variants in Level 2B clinical annotations are not in PharmGKB’s Tier 1 VIPs. These clinical annotations describe variant-drug combinations with a moderate level of evidence supporting the association. For example, the association may be found in multiple cohorts, but there may be a minority of studies that do not support the majority assertion. Level 2B clinical annotations must be supported by at least two independent publications. Drug-variant association: Efficacy

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

1.4

DANN

Benign

0.61

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000038

dbscSNV1_RF

Benign

0.0

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over