Variant 2-215312255-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_004044.7(ATIC):c.19+94G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00929 in 1,457,288 control chromosomes in the GnomAD database, including 110 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0077 ( 13 hom., cov: 33)

Exomes 𝑓: 0.0095 ( 97 hom. )

Consequence

ATIC
NM_004044.7 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.40

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.95).

BP6

Variant 2-215312255-G-A is Benign according to our data. Variant chr2-215312255-G-A is described in ClinVar as [Benign]. Clinvar id is 2651868.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.00948 (12376/1305028) while in subpopulation MID AF= 0.0435 (162/3726). AF 95% confidence interval is 0.038. There are 97 homozygotes in gnomad4_exome. There are 6195 alleles in male gnomad4_exome subpopulation. Median coverage is 29. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 13 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATIC	NM_004044.7 linkuse as main transcript	c.19+94G>A		intron_variant		ENST00000236959.14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATIC	ENST00000236959.14 linkuse as main transcript	c.19+94G>A		intron_variant		1	NM_004044.7	P1	P31939-1

Frequencies

GnomAD3 genomes

AF:

0.00771

AC:

1173

AN:

152150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00179

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0137

Gnomad ASJ

AF:

0.0432

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00372

Gnomad FIN

AF:

0.00151

Gnomad MID

AF:

0.0573

Gnomad NFE

AF:

0.00956

Gnomad OTH

AF:

0.0177

GnomAD3 exomes

AF:

0.0114

AC:

755

AN:

66442

Hom.:

AF XY:

0.0124

AC XY:

438

AN XY:

35390

show subpopulations

Gnomad AFR exome

AF:

0.00327

Gnomad AMR exome

AF:

0.0133

Gnomad ASJ exome

AF:

0.0677

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00709

Gnomad FIN exome

AF:

0.00150

Gnomad NFE exome

AF:

0.0127

Gnomad OTH exome

AF:

0.00994

GnomAD4 exome

AF:

0.00948

AC:

12376

AN:

1305028

Hom.:

Cov.:

AF XY:

0.00969

AC XY:

6195

AN XY:

639524

show subpopulations

Gnomad4 AFR exome

AF:

0.00199

Gnomad4 AMR exome

AF:

0.0124

Gnomad4 ASJ exome

AF:

0.0469

Gnomad4 EAS exome

AF:

0.0000287

Gnomad4 SAS exome

AF:

0.00542

Gnomad4 FIN exome

AF:

0.00259

Gnomad4 NFE exome

AF:

0.00941

Gnomad4 OTH exome

AF:

0.0125

GnomAD4 genome

AF:

0.00768

AC:

1169

AN:

152260

Hom.:

Cov.:

AF XY:

0.00763

AC XY:

568

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.00178

Gnomad4 AMR

AF:

0.0137

Gnomad4 ASJ

AF:

0.0432

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.00373

Gnomad4 FIN

AF:

0.00151

Gnomad4 NFE

AF:

0.00955

Gnomad4 OTH

AF:

0.0175

Alfa

AF:

0.00257

Hom.:

Bravo

AF:

0.00869

Asia WGS

AF:

0.00231

AC:

AN:

3474

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Feb 01, 2023

ATIC: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

3.9

DANN

Benign

0.92

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

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