chr2-215345513-C-T

Variant names:

• chr2-215345513-C-T
• rs16853834
• NM_004044.7:c.1320+642C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004044.7(ATIC):​c.1320+642C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.133 in 156,746 control chromosomes in the GnomAD database, including 1,770 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 0.13 (1708 hom., cov: 33)
  • Exomes 𝑓: 0.16 (62 hom.)
• Consequence: ATIC NM_004044.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.62
• Publications: 26 publications found

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]

ATIC Gene-Disease associations (from GenCC):

• AICA-ribosiduria

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.21 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004044.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATIC	NM_004044.7	MANE Select	c.1320+642C>T		intron	N/A	NP_004035.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATIC	ENST00000236959.14	TSL:1 MANE Select	c.1320+642C>T		intron	N/A	ENSP00000236959.9
	ATIC	ENST00000459796.1	TSL:3	n.773C>T		non_coding_transcript_exon	Exon 2 of 2
	ATIC	ENST00000435675.5	TSL:2	c.1317+642C>T		intron	N/A	ENSP00000415935.1

Frequencies

GnomAD3 genomes AF: 0.133 AC: 20170 AN: 152024 Hom.: 1710 Cov.: 33

Gnomad AFR AF: 0.0339

Gnomad AMI AF: 0.116

Gnomad AMR AF: 0.183

Gnomad ASJ AF: 0.186

Gnomad EAS AF: 0.220

Gnomad SAS AF: 0.223

Gnomad FIN AF: 0.157

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.161

Gnomad OTH AF: 0.151

GnomAD4 exome AF: 0.159 AC: 730 AN: 4602 Hom.: 62 Cov.: 0 AF XY: 0.164 AC XY: 403 AN XY: 2462

African (AFR) AF: 0.111 AC: 2 AN: 18

American (AMR) AF: 0.188 AC: 203 AN: 1080

Ashkenazi Jewish (ASJ) AF: 0.0714 AC: 1 AN: 14

East Asian (EAS) AF: 0.250 AC: 25 AN: 100

South Asian (SAS) AF: 0.201 AC: 83 AN: 412

European-Finnish (FIN) AF: 0.150 AC: 6 AN: 40

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4

European-Non Finnish (NFE) AF: 0.138 AC: 383 AN: 2784

Other (OTH) AF: 0.180 AC: 27 AN: 150

GnomAD4 genome AF: 0.132 AC: 20159 AN: 152144 Hom.: 1708 Cov.: 33 AF XY: 0.137 AC XY: 10160 AN XY: 74370

African (AFR) AF: 0.0338 AC: 1405 AN: 41536

American (AMR) AF: 0.183 AC: 2794 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.186 AC: 646 AN: 3470

East Asian (EAS) AF: 0.220 AC: 1136 AN: 5172

South Asian (SAS) AF: 0.221 AC: 1064 AN: 4804

European-Finnish (FIN) AF: 0.157 AC: 1664 AN: 10568

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.161 AC: 10972 AN: 67992

Other (OTH) AF: 0.149 AC: 314 AN: 2110

Alfa AF: 0.155 Hom.: 8776

Bravo AF: 0.130

Asia WGS AF: 0.201 AC: 700 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.0030
DANN	Benign	0.48
PhyloP100		-3.6
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs16853834; hg19: chr2-216210236;