rs1983462

chr2-215330558-G-A

Variant summary

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

The NM_004044.7(ATIC):c.689-1824G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.306 in 151,892 control chromosomes in the GnomAD database, including 7,694 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 0.31 (7694 hom., cov: 31)
• Consequence: ATIC NM_004044.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.78

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=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.389 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATIC	NM_004044.7	c.689-1824G>A		intron_variant		ENST00000236959.14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATIC	ENST00000236959.14	c.689-1824G>A		intron_variant		1	NM_004044.7	P1
ATIC	ENST00000435675.5	c.686-1824G>A		intron_variant		2
ATIC	ENST00000427397.5	c.*582-1824G>A		intron_variant, NMD_transcript_variant		5
ATIC	ENST00000443953.5	c.*786-1824G>A		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.306 AC: 46406 AN: 151774 Hom.: 7684 Cov.: 31

Gnomad AFR AF: 0.394

Gnomad AMI AF: 0.374

Gnomad AMR AF: 0.225

Gnomad ASJ AF: 0.211

Gnomad EAS AF: 0.00212

Gnomad SAS AF: 0.103

Gnomad FIN AF: 0.332

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.308

Gnomad OTH AF: 0.291

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

GnomAD4 genome AF: 0.306 AC: 46442 AN: 151892 Hom.: 7694 Cov.: 31 AF XY: 0.300 AC XY: 22263 AN XY: 74236

Gnomad4 AFR AF: 0.394

Gnomad4 AMR AF: 0.225

Gnomad4 ASJ AF: 0.211

Gnomad4 EAS AF: 0.00212

Gnomad4 SAS AF: 0.103

Gnomad4 FIN AF: 0.332

Gnomad4 NFE AF: 0.308

Gnomad4 OTH AF: 0.289

Alfa AF: 0.297 Hom.: 6881

Bravo AF: 0.302

Asia WGS AF: 0.0740 AC: 261 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.054
Dann	Benign	0.68

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: rs1983462; hg19: chr2-216195281;