2-215312255-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.40

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]

ACMG classification

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 GnomAd at 13 AR gene

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.00771 AC: 1173 AN: 152150 Hom.: 13 Cov.: 33

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.: 12 AF XY: 0.0124 AC XY: 438 AN XY: 35390

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.: 97 Cov.: 29 AF XY: 0.00969 AC XY: 6195 AN XY: 639524

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.: 13 Cov.: 33 AF XY: 0.00763 AC XY: 568 AN XY: 74450

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.: 2

Bravo AF: 0.00869

Asia WGS AF: 0.00231 AC: 9 AN: 3474

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

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

Other links and lift over

dbSNP: rs190514165; hg19: chr2-216176978;