2-215333248-T-C

Variant summary

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

The NM_004044.7(ATIC):c.815-102T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.543 in 922,674 control chromosomes in the GnomAD database, including 140,036 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 (18784 hom., cov: 33)
  • Exomes 𝑓: 0.56 (121252 hom.)
• Consequence: ATIC NM_004044.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.503

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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.756 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATIC	NM_004044.7	c.815-102T>C		intron_variant		ENST00000236959.14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATIC	ENST00000236959.14	c.815-102T>C		intron_variant		1	NM_004044.7	P1
ATIC	ENST00000435675.5	c.812-102T>C		intron_variant		2
ATIC	ENST00000427397.5	c.*708-102T>C		intron_variant, NMD_transcript_variant		5
ATIC	ENST00000443953.5	c.*912-102T>C		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.478 AC: 72620 AN: 151842 Hom.: 18749 Cov.: 33

Gnomad AFR AF: 0.286

Gnomad AMI AF: 0.519

Gnomad AMR AF: 0.559

Gnomad ASJ AF: 0.589

Gnomad EAS AF: 0.776

Gnomad SAS AF: 0.669

Gnomad FIN AF: 0.509

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.529

Gnomad OTH AF: 0.498

GnomAD4 exome AF: 0.556 AC: 428382 AN: 770712 Hom.: 121252 AF XY: 0.562 AC XY: 229063 AN XY: 407458

Gnomad4 AFR exome AF: 0.283

Gnomad4 AMR exome AF: 0.628

Gnomad4 ASJ exome AF: 0.587

Gnomad4 EAS exome AF: 0.719

Gnomad4 SAS exome AF: 0.679

Gnomad4 FIN exome AF: 0.520

Gnomad4 NFE exome AF: 0.534

Gnomad4 OTH exome AF: 0.555

GnomAD4 genome AF: 0.478 AC: 72701 AN: 151962 Hom.: 18784 Cov.: 33 AF XY: 0.482 AC XY: 35817 AN XY: 74294

Gnomad4 AFR AF: 0.286

Gnomad4 AMR AF: 0.560

Gnomad4 ASJ AF: 0.589

Gnomad4 EAS AF: 0.776

Gnomad4 SAS AF: 0.671

Gnomad4 FIN AF: 0.509

Gnomad4 NFE AF: 0.529

Gnomad4 OTH AF: 0.503

Alfa AF: 0.531 Hom.: 36568

Bravo AF: 0.473

Asia WGS AF: 0.702 AC: 2438 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	0.53
Dann	Benign	0.73

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: rs12995526; hg19: chr2-216197971; COSMIC: COSV52694555; COSMIC: COSV52694555;