Variant 2-215325969-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_004044.7(ATIC):c.380-18G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000985 in 1,613,696 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0051 ( 6 hom., cov: 32)

Exomes 𝑓: 0.00056 ( 9 hom. )

Consequence

ATIC
NM_004044.7 intron

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -2.13

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 2-215325969-G-A is Benign according to our data. Variant chr2-215325969-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 445428.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00511 (778/152246) while in subpopulation AFR AF= 0.0179 (743/41540). AF 95% confidence interval is 0.0168. There are 6 homozygotes in gnomad4. There are 376 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATIC	NM_004044.7 linkuse as main transcript	c.380-18G>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.380-18G>A		intron_variant		1	NM_004044.7	P1	P31939-1

Frequencies

GnomAD3 genomes

AF:

0.00511

AC:

778

AN:

152128

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0179

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00170

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:

0.0000294

Gnomad OTH

AF:

0.00335

GnomAD3 exomes

AF:

0.00149

AC:

371

AN:

249810

Hom.:

AF XY:

0.00114

AC XY:

154

AN XY:

135182

show subpopulations

Gnomad AFR exome

AF:

0.0196

Gnomad AMR exome

AF:

0.000925

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000134

Gnomad OTH exome

AF:

0.000816

GnomAD4 exome

AF:

0.000556

AC:

812

AN:

1461450

Hom.:

Cov.:

AF XY:

0.000483

AC XY:

351

AN XY:

727040

show subpopulations

Gnomad4 AFR exome

AF:

0.0184

Gnomad4 AMR exome

AF:

0.00110

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000928

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000468

Gnomad4 OTH exome

AF:

0.00139

GnomAD4 genome

AF:

0.00511

AC:

778

AN:

152246

Hom.:

Cov.:

AF XY:

0.00505

AC XY:

376

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.0179

Gnomad4 AMR

AF:

0.00170

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00332

Alfa

AF:

0.00294

Hom.:

Bravo

AF:

0.00624

Asia WGS

AF:

0.00173

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	May 04, 2017	- -

AICA-ribosiduria

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Apr 11, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.020

DANN

Benign

0.61

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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