dbSNP rs4817580: GART:c.-9+296C>T (chr21-33542291-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000381831.7(GART):c.-9+296C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0994 in 152,302 control chromosomes in the GnomAD database, including 1,001 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 0.099 ( 1001 hom., cov: 32)

Exomes 𝑓: 0.090 ( 0 hom. )

Consequence

GART
ENST00000381831.7 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.662

Publications

8 publications found

Variant links:

Genes affected

GART (HGNC:4163): (phosphoribosylglycinamide formyltransferase, phosphoribosylglycinamide synthetase, phosphoribosylaminoimidazole synthetase) The protein encoded by this gene is a trifunctional polypeptide. It has phosphoribosylglycinamide formyltransferase, phosphoribosylglycinamide synthetase, phosphoribosylaminoimidazole synthetase activity which is required for de novo purine biosynthesis. This enzyme is highly conserved in vertebrates. Alternative splicing of this gene results in two transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

GART 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=-0.78).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.247 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GART	NM_000819.5 link	c.-268C>T		upstream_gene_variant		ENST00000381815.9	NP_000810.1	P22102-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GART	ENST00000381815.9 link	c.-268C>T		upstream_gene_variant		1	NM_000819.5	ENSP00000371236.4		P22102-1

Frequencies

GnomAD3 genomes

AF:

0.0993

AC:

15103

AN:

152084

Hom.:

992

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0324

Gnomad AMI

AF:

0.0329

Gnomad AMR

AF:

0.154

Gnomad ASJ

AF:

0.148

Gnomad EAS

AF:

0.258

Gnomad SAS

AF:

0.117

Gnomad FIN

AF:

0.129

Gnomad MID

AF:

0.123

Gnomad NFE

AF:

0.108

Gnomad OTH

AF:

0.0987

GnomAD4 exome

AF:

0.0900

AC:

AN:

100

Hom.:

Cov.:

AF XY:

0.0676

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.125

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.250

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0690

AC:

AN:

Other (OTH)

AF:

0.250

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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:

0.0994

AC:

15130

AN:

152202

Hom.:

1001

Cov.:

AF XY:

0.102

AC XY:

7558

AN XY:

74414

show subpopulations

African (AFR)

AF:

0.0324

AC:

1346

AN:

41560

American (AMR)

AF:

0.155

AC:

2368

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.148

AC:

514

AN:

3470

East Asian (EAS)

AF:

0.258

AC:

1336

AN:

5170

South Asian (SAS)

AF:

0.118

AC:

567

AN:

4822

European-Finnish (FIN)

AF:

0.129

AC:

1363

AN:

10602

Middle Eastern (MID)

AF:

0.119

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.108

AC:

7345

AN:

67976

Other (OTH)

AF:

0.107

AC:

226

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

668

1336

2003

2671

3339

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

178

356

534

712

890

<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:

0.0983

Hom.:

143

Bravo

AF:

0.102

Asia WGS

AF:

0.199

AC:

692

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

6.6

(source)

DANN

Benign

0.80

PhyloP100

0.66

PromoterAI

0.022

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over