rs7604984

Variant names:

• chr2-215352916-G-A
• rs7604984
• XM_047444489.1:c.1787+835G>A

Your query was ambiguous. Multiple possible variants found:

• chr2-215352916-G-A
• chr2-215352916-G-C

Variant summary

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

The XM_047444489.1(ATIC):​c.1787+835G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.59 in 152,004 control chromosomes in the GnomAD database, including 26,552 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 0.59 (26552 hom., cov: 32)
• Consequence: ATIC XM_047444489.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.538
• Publications: 15 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.7 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATIC	XM_047444489.1	c.1787+835G>A		intron_variant	Intron 16 of 16		XP_047300445.1
ATIC	XM_047444490.1	c.1787+835G>A		intron_variant	Intron 16 of 16		XP_047300446.1
ATIC	XM_017004187.3	c.1659+3667G>A		intron_variant	Intron 15 of 15		XP_016859676.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.590 AC: 89583 AN: 151886 Hom.: 26547 Cov.: 32

Gnomad AFR AF: 0.563

Gnomad AMI AF: 0.566

Gnomad AMR AF: 0.604

Gnomad ASJ AF: 0.491

Gnomad EAS AF: 0.720

Gnomad SAS AF: 0.466

Gnomad FIN AF: 0.609

Gnomad MID AF: 0.563

Gnomad NFE AF: 0.604

Gnomad OTH AF: 0.590

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.590 AC: 89622 AN: 152004 Hom.: 26552 Cov.: 32 AF XY: 0.588 AC XY: 43714 AN XY: 74286

African (AFR) AF: 0.563 AC: 23303 AN: 41416

American (AMR) AF: 0.604 AC: 9221 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.491 AC: 1704 AN: 3472

East Asian (EAS) AF: 0.719 AC: 3707 AN: 5154

South Asian (SAS) AF: 0.464 AC: 2237 AN: 4818

European-Finnish (FIN) AF: 0.609 AC: 6430 AN: 10550

Middle Eastern (MID) AF: 0.571 AC: 168 AN: 294

European-Non Finnish (NFE) AF: 0.604 AC: 41093 AN: 68002

Other (OTH) AF: 0.589 AC: 1243 AN: 2110

Alfa AF: 0.591 Hom.: 85021

Bravo AF: 0.587

Asia WGS AF: 0.552 AC: 1923 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.025
DANN	Benign	0.74
PhyloP100		-0.54

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs7604984; hg19: chr2-216217639;