rs2070388

Variant names:

• chr21-33504401-G-C
• rs2070388
• NM_000819.5:c.2841+11C>G

Your query was ambiguous. Multiple possible variants found:

• chr21-33504401-G-C
• chr21-33504401-G-T

Variant summary

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

The NM_000819.5(GART):​c.2841+11C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.106 in 1,610,698 control chromosomes in the GnomAD database, including 10,573 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 0.092 (896 hom., cov: 32)
  • Exomes 𝑓: 0.11 (9677 hom.)
• Consequence: GART NM_000819.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.283
• Publications: 10 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.241 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GART	NM_000819.5	c.2841+11C>G		intron_variant	Intron 21 of 21	ENST00000381815.9	NP_000810.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GART	ENST00000381815.9	c.2841+11C>G		intron_variant	Intron 21 of 21	1	NM_000819.5	ENSP00000371236.4
GART	ENST00000381831.7	c.2841+11C>G		intron_variant	Intron 21 of 21	1		ENSP00000371253.3
GART	ENST00000381839.7	c.2841+11C>G		intron_variant	Intron 21 of 21	1		ENSP00000371261.3
GART	ENST00000424203.5	n.*1924+11C>G		intron_variant	Intron 21 of 21	1		ENSP00000390003.1

Frequencies

GnomAD3 genomes AF: 0.0920 AC: 13995 AN: 152050 Hom.: 887 Cov.: 32

Gnomad AFR AF: 0.0218

Gnomad AMI AF: 0.0318

Gnomad AMR AF: 0.149

Gnomad ASJ AF: 0.119

Gnomad EAS AF: 0.253

Gnomad SAS AF: 0.118

Gnomad FIN AF: 0.127

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.102

Gnomad OTH AF: 0.0890

GnomAD2 exomes AF: 0.130 AC: 32725 AN: 251114 AF XY: 0.126

Gnomad AFR exome AF: 0.0191

Gnomad AMR exome AF: 0.227

Gnomad ASJ exome AF: 0.104

Gnomad EAS exome AF: 0.248

Gnomad FIN exome AF: 0.132

Gnomad NFE exome AF: 0.104

Gnomad OTH exome AF: 0.112

GnomAD4 exome AF: 0.108 AC: 157239 AN: 1458530 Hom.: 9677 Cov.: 30 AF XY: 0.108 AC XY: 78317 AN XY: 725274

African (AFR) AF: 0.0171 AC: 572 AN: 33424

American (AMR) AF: 0.219 AC: 9777 AN: 44610

Ashkenazi Jewish (ASJ) AF: 0.110 AC: 2883 AN: 26098

East Asian (EAS) AF: 0.237 AC: 9384 AN: 39626

South Asian (SAS) AF: 0.116 AC: 9980 AN: 86198

European-Finnish (FIN) AF: 0.131 AC: 6990 AN: 53410

Middle Eastern (MID) AF: 0.122 AC: 705 AN: 5756

European-Non Finnish (NFE) AF: 0.0996 AC: 110472 AN: 1109152

Other (OTH) AF: 0.107 AC: 6476 AN: 60256

GnomAD4 genome AF: 0.0921 AC: 14020 AN: 152168 Hom.: 896 Cov.: 32 AF XY: 0.0944 AC XY: 7022 AN XY: 74386

African (AFR) AF: 0.0217 AC: 903 AN: 41548

American (AMR) AF: 0.149 AC: 2277 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.119 AC: 414 AN: 3472

East Asian (EAS) AF: 0.253 AC: 1305 AN: 5168

South Asian (SAS) AF: 0.118 AC: 570 AN: 4820

European-Finnish (FIN) AF: 0.127 AC: 1342 AN: 10582

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.102 AC: 6941 AN: 67990

Other (OTH) AF: 0.0975 AC: 206 AN: 2112

Alfa AF: 0.0964 Hom.: 158

Bravo AF: 0.0942

Asia WGS AF: 0.197 AC: 686 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	17
DANN	Benign	0.58
PhyloP100		0.28
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		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: rs2070388; hg19: chr21-34876708; COSMIC: COSV67818244; COSMIC: COSV67818244;