rs1404772

Positions:

• chr2-215345576-C-A
• chr2-215345576-C-G
• chr2-215345576-C-T

Variant summary

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

The NM_004044.7(ATIC):​c.1320+705C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.928 in 153,296 control chromosomes in the GnomAD database, including 66,025 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 0.93 (65548 hom., cov: 32)
  • Exomes 𝑓: 0.95 (477 hom.)
• Consequence: ATIC NM_004044.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.42

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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATIC	NM_004044.7	c.1320+705C>A		intron_variant		ENST00000236959.14	NP_004035.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATIC	ENST00000236959.14	c.1320+705C>A		intron_variant		1	NM_004044.7	ENSP00000236959	P1

Frequencies

GnomAD3 genomes AF: 0.928 AC: 141153 AN: 152112 Hom.: 65514 Cov.: 32

Gnomad AFR AF: 0.930

Gnomad AMI AF: 0.952

Gnomad AMR AF: 0.934

Gnomad ASJ AF: 0.853

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.938

Gnomad FIN AF: 0.880

Gnomad MID AF: 0.908

Gnomad NFE AF: 0.930

Gnomad OTH AF: 0.924

GnomAD4 exome AF: 0.947 AC: 1010 AN: 1066 Hom.: 477 Cov.: 0 AF XY: 0.938 AC XY: 531 AN XY: 566

Gnomad4 AFR exome AF: 1.00

Gnomad4 AMR exome AF: 0.934

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.932

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 0.952

Gnomad4 OTH exome AF: 0.889

GnomAD4 genome AF: 0.928 AC: 141243 AN: 152230 Hom.: 65548 Cov.: 32 AF XY: 0.925 AC XY: 68876 AN XY: 74424

Gnomad4 AFR AF: 0.930

Gnomad4 AMR AF: 0.934

Gnomad4 ASJ AF: 0.853

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.937

Gnomad4 FIN AF: 0.880

Gnomad4 NFE AF: 0.930

Gnomad4 OTH AF: 0.925

Alfa AF: 0.928 Hom.: 86521

Bravo AF: 0.931

Asia WGS AF: 0.964 AC: 3354 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.071
DANN	Benign	0.44

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: rs1404772; hg19: chr2-216210299;