rs4817580

Positions:

• chr21-33542291-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.662

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

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
GART	NM_001136005.1	c.-9+296C>T		intron_variant			NP_001129477.1
GART	NM_001136006.1	c.-42+369C>T		intron_variant			NP_001129478.1
GART	XM_005260941.3	c.-42+257C>T		intron_variant			XP_005260998.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GART	ENST00000381831.7	c.-9+296C>T		intron_variant		1		ENSP00000371253	P1
GART	ENST00000381839.7	c.-42+369C>T		intron_variant		1		ENSP00000371261	P1
GART	ENST00000424203.5	c.-42+300C>T		intron_variant, NMD_transcript_variant		1		ENSP00000390003

Frequencies

GnomAD3 genomes AF: 0.0993 AC: 15103 AN: 152084 Hom.: 992 Cov.: 32

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: 9 AN: 100 Hom.: 0 Cov.: 0 AF XY: 0.0676 AC XY: 5 AN XY: 74

Gnomad4 AFR exome AF: 0.125

Gnomad4 ASJ exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.250

Gnomad4 NFE exome AF: 0.0690

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.0994 AC: 15130 AN: 152202 Hom.: 1001 Cov.: 32 AF XY: 0.102 AC XY: 7558 AN XY: 74414

Gnomad4 AFR AF: 0.0324

Gnomad4 AMR AF: 0.155

Gnomad4 ASJ AF: 0.148

Gnomad4 EAS AF: 0.258

Gnomad4 SAS AF: 0.118

Gnomad4 FIN AF: 0.129

Gnomad4 NFE AF: 0.108

Gnomad4 OTH AF: 0.107

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
DANN	Benign	0.80

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4817580; hg19: chr21-34914597;