Variant chr2-215319722-A-G 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.281A>G(p.Asn94Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000926 in 1,608,548 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0047 ( 5 hom., cov: 32)

Exomes 𝑓: 0.00053 ( 6 hom. )

Consequence

ATIC
NM_004044.7 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.384

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 (MetaRNN=0.004313916).

BP6

Variant 2-215319722-A-G is Benign according to our data. Variant chr2-215319722-A-G is described in ClinVar as [Benign]. Clinvar id is 791888.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-215319722-A-G is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00468 (712/152280) while in subpopulation AFR AF= 0.0163 (676/41562). AF 95% confidence interval is 0.0152. There are 5 homozygotes in gnomad4. There are 337 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATIC	NM_004044.7 linkuse as main transcript	c.281A>G	p.Asn94Ser	missense_variant	4/16	ENST00000236959.14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATIC	ENST00000236959.14 linkuse as main transcript	c.281A>G	p.Asn94Ser	missense_variant	4/16	1	NM_004044.7	P1	P31939-1

Frequencies

GnomAD3 genomes

AF:

0.00467

AC:

710

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0163

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00157

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00125

AC:

314

AN:

251254

Hom.:

AF XY:

0.000942

AC XY:

128

AN XY:

135832

show subpopulations

Gnomad AFR exome

AF:

0.0169

Gnomad AMR exome

AF:

0.000318

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000817

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000880

Gnomad OTH exome

AF:

0.000490

GnomAD4 exome

AF:

0.000534

AC:

778

AN:

1456268

Hom.:

Cov.:

AF XY:

0.000490

AC XY:

355

AN XY:

724938

show subpopulations

Gnomad4 AFR exome

AF:

0.0188

Gnomad4 AMR exome

AF:

0.000537

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000685

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000903

Gnomad4 OTH exome

AF:

0.000913

GnomAD4 genome

AF:

0.00468

AC:

712

AN:

152280

Hom.:

Cov.:

AF XY:

0.00453

AC XY:

337

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.0163

Gnomad4 AMR

AF:

0.00157

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.000584

Hom.:

Bravo

AF:

0.00537

ESP6500AA

AF:

0.0127

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00167

AC:

203

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

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

Labcorp Genetics (formerly Invitae), Labcorp

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.056

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.53

CADD

Benign

0.63

DANN

Benign

0.51

DEOGEN2

Benign

0.15

T;.;.

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.35

LIST_S2

Benign

0.75

T;T;T

MetaRNN

Benign

0.0043

T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

-1.1

N;.;.

MutationTaster

Benign

0.95

D;N;N

PrimateAI

Benign

0.31

PROVEAN

Benign

0.38

N;N;N

REVEL

Benign

0.24

Sift

Benign

0.65

T;T;T

Sift4G

Benign

0.62

T;T;T

Polyphen

0.0

B;.;.

Vest4

0.18

MVP

0.31

MPC

0.045

ClinPred

0.0015

GERP RS

-6.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.043

gMVP

0.27

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