rs1404772

Variant names:

• chr2-215345576-C-A
• rs1404772
• NM_004044.7:c.1320+705C>A

Your query was ambiguous. Multiple possible variants found:

• chr2-215345576-C-A
• chr2-215345576-C-G
• chr2-215345576-C-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+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
• Publications: 7 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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 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+705C>A		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+705C>A		intron	N/A	ENSP00000236959.9
	ATIC	ENST00000459796.1	TSL:3	n.836C>A		non_coding_transcript_exon	Exon 2 of 2
	ATIC	ENST00000435675.5	TSL:2	c.1317+705C>A		intron	N/A	ENSP00000415935.1

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

African (AFR) AF: 1.00 AC: 6 AN: 6

American (AMR) AF: 0.934 AC: 155 AN: 166

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 1.00 AC: 10 AN: 10

South Asian (SAS) AF: 0.932 AC: 41 AN: 44

European-Finnish (FIN) AF: 1.00 AC: 6 AN: 6

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.952 AC: 760 AN: 798

Other (OTH) AF: 0.889 AC: 32 AN: 36

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

African (AFR) AF: 0.930 AC: 38644 AN: 41548

American (AMR) AF: 0.934 AC: 14286 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.853 AC: 2961 AN: 3472

East Asian (EAS) AF: 0.999 AC: 5175 AN: 5182

South Asian (SAS) AF: 0.937 AC: 4518 AN: 4822

European-Finnish (FIN) AF: 0.880 AC: 9319 AN: 10586

Middle Eastern (MID) AF: 0.901 AC: 265 AN: 294

European-Non Finnish (NFE) AF: 0.930 AC: 63253 AN: 68012

Other (OTH) AF: 0.925 AC: 1954 AN: 2112

Alfa AF: 0.929 Hom.: 109801

Bravo AF: 0.931

Asia WGS AF: 0.964 AC: 3354 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.071
DANN	Benign	0.44
PhyloP100		-4.4
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: rs1404772; hg19: chr2-216210299;