NM_004044.7:c.147-111A>T

Variant names:

• chr2-215318046-A-T
• rs4672766
• NM_004044.7:c.147-111A>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_004044.7(ATIC):​c.147-111A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 1 in 940,902 control chromosomes in the GnomAD database, including 470,382 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 1.0 (76134 hom., cov: 33)
  • Exomes 𝑓: 1.0 (394248 hom.)
• Consequence: ATIC NM_004044.7 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.985
• Publications: 4 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: Orphanet, Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BP6: Variant 2-215318046-A-T is Benign according to our data. Variant chr2-215318046-A-T is described in ClinVar as Benign. ClinVar VariationId is 1192367.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.994 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATIC	NM_004044.7	MANE Select	c.147-111A>T		intron	N/A	NP_004035.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATIC	ENST00000236959.14	TSL:1 MANE Select	c.147-111A>T		intron	N/A	ENSP00000236959.9	P31939-1
	ATIC	ENST00000435675.5	TSL:2	c.144-111A>T		intron	N/A	ENSP00000415935.1	P31939-2
	ATIC	ENST00000957330.1		c.147-111A>T		intron	N/A	ENSP00000627389.1

Frequencies

GnomAD3 genomes AF: 1.00 AC: 152194 AN: 152232 Hom.: 76078 Cov.: 33

Gnomad AFR AF: 0.999

Gnomad AMI AF: 1.00

Gnomad AMR AF: 1.00

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 1.00

Gnomad SAS AF: 1.00

Gnomad FIN AF: 1.00

Gnomad MID AF: 1.00

Gnomad NFE AF: 1.00

Gnomad OTH AF: 1.00

GnomAD4 exome AF: 1.00 AC: 788524 AN: 788552 Hom.: 394248 AF XY: 1.00 AC XY: 412724 AN XY: 412742

African (AFR) AF: 0.999 AC: 19708 AN: 19726

American (AMR) AF: 1.00 AC: 39635 AN: 39638

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 21586 AN: 21586

East Asian (EAS) AF: 1.00 AC: 35148 AN: 35148

South Asian (SAS) AF: 1.00 AC: 68385 AN: 68386

European-Finnish (FIN) AF: 1.00 AC: 49841 AN: 49842

Middle Eastern (MID) AF: 1.00 AC: 4424 AN: 4424

European-Non Finnish (NFE) AF: 1.00 AC: 511907 AN: 511908

Other (OTH) AF: 1.00 AC: 37890 AN: 37894

GnomAD4 genome AF: 1.00 AC: 152309 AN: 152350 Hom.: 76134 Cov.: 33 AF XY: 1.00 AC XY: 74486 AN XY: 74502

African (AFR) AF: 0.999 AC: 41537 AN: 41576

American (AMR) AF: 1.00 AC: 15290 AN: 15292

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 3472 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5192 AN: 5192

South Asian (SAS) AF: 1.00 AC: 4832 AN: 4832

European-Finnish (FIN) AF: 1.00 AC: 10620 AN: 10620

Middle Eastern (MID) AF: 1.00 AC: 294 AN: 294

European-Non Finnish (NFE) AF: 1.00 AC: 68046 AN: 68046

Other (OTH) AF: 1.00 AC: 2114 AN: 2114

Alfa AF: 1.00 Hom.: 9294

Bravo AF: 1.00

Asia WGS AF: 0.999 AC: 3473 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	AICA-ribosiduria (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.91
DANN	Benign	0.23
PhyloP100		-0.98
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: rs4672766; hg19: chr2-216182769;