dbSNP rs1404772: ATIC:c.1320+705C>A (chr2-215345576-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -4.42

Publications

7 publications found

Variant links:

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: G2P, Orphanet, Labcorp Genetics (formerly Invitae)

ATIC links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

Sel.	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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ATIC	ENST00000236959.14	TSL:1 MANE Select	c.1320+705C>A	intron	N/A	ENSP00000236959.9	P31939-1
ATIC	ENST00000435675.5	TSL:2	c.1317+705C>A	intron	N/A	ENSP00000415935.1	P31939-2
ATIC	ENST00000957330.1		c.1320+705C>A	intron	N/A	ENSP00000627389.1

Frequencies

GnomAD3 genomes

AF:

0.928

AC:

141153

AN:

152112

Hom.:

65514

Cov.:

show subpopulations

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.:

AF XY:

0.938

AC XY:

531

AN XY:

566

show subpopulations

African (AFR)

AF:

1.00

AC:

AN:

American (AMR)

AF:

0.934

AC:

155

AN:

166

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

1.00

AC:

AN:

South Asian (SAS)

AF:

0.932

AC:

AN:

European-Finnish (FIN)

AF:

1.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.952

AC:

760

AN:

798

Other (OTH)

AF:

0.889

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.551

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.928

AC:

141243

AN:

152230

Hom.:

65548

Cov.:

AF XY:

0.925

AC XY:

68876

AN XY:

74424

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

531

1062

1594

2125

2656

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

906

1812

2718

3624

4530

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

(source)

DANN

Benign

0.44

PhyloP100

-4.4

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over