chr2-215321102-C-T

Position:

• chr2-215321102-C-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.290+1371C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.211 in 152,126 control chromosomes in the GnomAD database, including 4,299 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.21 (4299 hom., cov: 32)
• Consequence: ATIC NM_004044.7 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.401

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=-0.82).
• BP6: Variant 2-215321102-C-T is Benign according to our data. Variant chr2-215321102-C-T is described in ClinVar as [Benign]. Clinvar id is 1545064.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.297 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATIC	NM_004044.7	c.290+1371C>T		intron_variant		ENST00000236959.14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATIC	ENST00000236959.14	c.290+1371C>T		intron_variant		1	NM_004044.7	P1

Frequencies

GnomAD3 genomes AF: 0.211 AC: 32062 AN: 152008 Hom.: 4300 Cov.: 32

Gnomad AFR AF: 0.0857

Gnomad AMI AF: 0.365

Gnomad AMR AF: 0.183

Gnomad ASJ AF: 0.202

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.0594

Gnomad FIN AF: 0.329

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.300

Gnomad OTH AF: 0.213

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

GnomAD4 genome AF: 0.211 AC: 32056 AN: 152126 Hom.: 4299 Cov.: 32 AF XY: 0.207 AC XY: 15398 AN XY: 74356

Gnomad4 AFR AF: 0.0856

Gnomad4 AMR AF: 0.183

Gnomad4 ASJ AF: 0.202

Gnomad4 EAS AF: 0.00154

Gnomad4 SAS AF: 0.0597

Gnomad4 FIN AF: 0.329

Gnomad4 NFE AF: 0.300

Gnomad4 OTH AF: 0.211

Alfa AF: 0.271 Hom.: 7869

Bravo AF: 0.196

Asia WGS AF: 0.0330 AC: 117 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

Labcorp Genetics (formerly Invitae), Labcorp

Jan 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.14
DANN	Benign	0.88
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs10197559; hg19: chr2-216185825;