rs16853826

Positions:

• chr2-215340444-G-A
• chr2-215340444-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_004044.7(ATIC):​c.1227+1537G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.155 in 152,126 control chromosomes in the GnomAD database, including 2,145 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.16 (2145 hom., cov: 32)
• Consequence: ATIC NM_004044.7 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.209

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=-0.86).
• BP6: Variant 2-215340444-G-A is Benign according to our data. Variant chr2-215340444-G-A is described in ClinVar as [Benign]. Clinvar id is 1545046.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.481 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATIC	NM_004044.7	c.1227+1537G>A		intron_variant		ENST00000236959.14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATIC	ENST00000236959.14	c.1227+1537G>A		intron_variant		1	NM_004044.7	P1

Frequencies

GnomAD3 genomes AF: 0.155 AC: 23560 AN: 152006 Hom.: 2140 Cov.: 32

Gnomad AFR AF: 0.151

Gnomad AMI AF: 0.0844

Gnomad AMR AF: 0.193

Gnomad ASJ AF: 0.0934

Gnomad EAS AF: 0.497

Gnomad SAS AF: 0.140

Gnomad FIN AF: 0.118

Gnomad MID AF: 0.134

Gnomad NFE AF: 0.134

Gnomad OTH AF: 0.145

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.155 AC: 23587 AN: 152126 Hom.: 2145 Cov.: 32 AF XY: 0.156 AC XY: 11602 AN XY: 74374

Gnomad4 AFR AF: 0.151

Gnomad4 AMR AF: 0.193

Gnomad4 ASJ AF: 0.0934

Gnomad4 EAS AF: 0.497

Gnomad4 SAS AF: 0.139

Gnomad4 FIN AF: 0.118

Gnomad4 NFE AF: 0.134

Gnomad4 OTH AF: 0.148

Alfa AF: 0.142 Hom.: 496

Bravo AF: 0.162

Asia WGS AF: 0.281 AC: 976 AN: 3478

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

Invitae

Jan 24, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.0
DANN	Benign	0.64
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
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

Other links and lift over

dbSNP: rs16853826; hg19: chr2-216205167;