chr2-215331322-G-T

Position:

• chr2-215331322-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004044.7(ATIC):​c.689-1060G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.484 in 150,510 control chromosomes in the GnomAD database, including 18,903 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.48 (18903 hom., cov: 29)
• Consequence: ATIC NM_004044.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.376

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.761 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATIC	NM_004044.7	c.689-1060G>T		intron_variant		ENST00000236959.14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATIC	ENST00000236959.14	c.689-1060G>T		intron_variant		1	NM_004044.7	P1
ATIC	ENST00000435675.5	c.686-1060G>T		intron_variant		2
ATIC	ENST00000427397.5	c.*582-1060G>T		intron_variant, NMD_transcript_variant		5
ATIC	ENST00000443953.5	c.*786-1060G>T		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.484 AC: 72740 AN: 150412 Hom.: 18873 Cov.: 29

Gnomad AFR AF: 0.300

Gnomad AMI AF: 0.534

Gnomad AMR AF: 0.561

Gnomad ASJ AF: 0.590

Gnomad EAS AF: 0.780

Gnomad SAS AF: 0.672

Gnomad FIN AF: 0.509

Gnomad MID AF: 0.565

Gnomad NFE AF: 0.530

Gnomad OTH AF: 0.504

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

GnomAD4 genome AF: 0.484 AC: 72813 AN: 150510 Hom.: 18903 Cov.: 29 AF XY: 0.487 AC XY: 35706 AN XY: 73322

Gnomad4 AFR AF: 0.301

Gnomad4 AMR AF: 0.561

Gnomad4 ASJ AF: 0.590

Gnomad4 EAS AF: 0.781

Gnomad4 SAS AF: 0.674

Gnomad4 FIN AF: 0.509

Gnomad4 NFE AF: 0.530

Gnomad4 OTH AF: 0.510

Alfa AF: 0.515 Hom.: 8260

Bravo AF: 0.479

Asia WGS AF: 0.702 AC: 2436 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.8
DANN	Benign	0.64

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: rs13005416; hg19: chr2-216196045;