chr2-215319657-T-A

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_004044.7(ATIC):​c.224-8T>A variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00045 in 1,603,986 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0019 ( 2 hom., cov: 32)
Exomes 𝑓: 0.00030 ( 2 hom. )

Consequence

ATIC
NM_004044.7 splice_region, splice_polypyrimidine_tract, intron

Scores

2
Splicing: ADA: 0.002993
2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.150
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.8).
BP6
Variant 2-215319657-T-A is Benign according to our data. Variant chr2-215319657-T-A is described in ClinVar as [Benign]. Clinvar id is 772858.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS2
High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ATICNM_004044.7 linkuse as main transcriptc.224-8T>A splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant ENST00000236959.14

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ATICENST00000236959.14 linkuse as main transcriptc.224-8T>A splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant 1 NM_004044.7 P1P31939-1

Frequencies

GnomAD3 genomes
AF:
0.00189
AC:
288
AN:
152212
Hom.:
2
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00639
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000785
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000882
Gnomad OTH
AF:
0.00239
GnomAD3 exomes
AF:
0.000613
AC:
154
AN:
251168
Hom.:
0
AF XY:
0.000442
AC XY:
60
AN XY:
135798
show subpopulations
Gnomad AFR exome
AF:
0.00766
Gnomad AMR exome
AF:
0.000260
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000196
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000114
Gnomad OTH exome
AF:
0.000327
GnomAD4 exome
AF:
0.000298
AC:
432
AN:
1451656
Hom.:
2
Cov.:
30
AF XY:
0.000248
AC XY:
179
AN XY:
723008
show subpopulations
Gnomad4 AFR exome
AF:
0.00860
Gnomad4 AMR exome
AF:
0.000358
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000505
Gnomad4 SAS exome
AF:
0.000105
Gnomad4 FIN exome
AF:
0.0000374
Gnomad4 NFE exome
AF:
0.0000753
Gnomad4 OTH exome
AF:
0.000533
GnomAD4 genome
AF:
0.00190
AC:
290
AN:
152330
Hom.:
2
Cov.:
32
AF XY:
0.00184
AC XY:
137
AN XY:
74502
show subpopulations
Gnomad4 AFR
AF:
0.00642
Gnomad4 AMR
AF:
0.000784
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000882
Gnomad4 OTH
AF:
0.00237
Alfa
AF:
0.000848
Hom.:
0
Bravo
AF:
0.00244
Asia WGS
AF:
0.000289
AC:
1
AN:
3478
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

ATIC-related disorder Benign:1
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesJan 22, 2020This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeNov 22, 2023- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.80
CADD
Benign
2.9
DANN
Benign
0.60

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.0030
dbscSNV1_RF
Benign
0.13
SpliceAI score (max)
0.010
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.

Other links and lift over

dbSNP: rs114443266; hg19: chr2-216184380; API