rs2422862

chr20-3219057-G-Achr20-3219057-G-C

Variant summary

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

The NM_033453.4(ITPA):c.411+425G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.887 in 209,088 control chromosomes in the GnomAD database, including 82,711 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 0.89 (61057 hom., cov: 30)
  • Exomes 𝑓: 0.87 (21654 hom.)
• Consequence: ITPA NM_033453.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.823

Genes affected

ITPA (HGNC:6176): (inosine triphosphatase) This gene encodes an inosine triphosphate pyrophosphohydrolase. The encoded protein hydrolyzes inosine triphosphate and deoxyinosine triphosphate to the monophosphate nucleotide and diphosphate. This protein, which is a member of the HAM1 NTPase protein family, is found in the cytoplasm and acts as a homodimer. Defects in the encoded protein can result in inosine triphosphate pyrophosphorylase deficiency which causes an accumulation of ITP in red blood cells. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Jun 2012]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ITPA	NM_033453.4	c.411+425G>A		intron_variant		ENST00000380113.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ITPA	ENST00000380113.8	c.411+425G>A		intron_variant		1	NM_033453.4	P1

Frequencies

GnomAD3 genomes AF: 0.894 AC: 135869 AN: 151924 Hom.: 60993 Cov.: 30

Gnomad AFR AF: 0.961

Gnomad AMI AF: 0.900

Gnomad AMR AF: 0.919

Gnomad ASJ AF: 0.803

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.903

Gnomad FIN AF: 0.829

Gnomad MID AF: 0.758

Gnomad NFE AF: 0.855

Gnomad OTH AF: 0.893

GnomAD4 exome AF: 0.868 AC: 49541 AN: 57046 Hom.: 21654 Cov.: 0 AF XY: 0.870 AC XY: 26314 AN XY: 30232

Gnomad4 AFR exome AF: 0.956

Gnomad4 AMR exome AF: 0.927

Gnomad4 ASJ exome AF: 0.808

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.885

Gnomad4 FIN exome AF: 0.839

Gnomad4 NFE exome AF: 0.849

Gnomad4 OTH exome AF: 0.863

GnomAD4 genome AF: 0.894 AC: 135994 AN: 152042 Hom.: 61057 Cov.: 30 AF XY: 0.895 AC XY: 66490 AN XY: 74310

Gnomad4 AFR AF: 0.961

Gnomad4 AMR AF: 0.919

Gnomad4 ASJ AF: 0.803

Gnomad4 EAS AF: 0.998

Gnomad4 SAS AF: 0.903

Gnomad4 FIN AF: 0.829

Gnomad4 NFE AF: 0.855

Gnomad4 OTH AF: 0.894

Alfa AF: 0.865 Hom.: 32424

Bravo AF: 0.902

Asia WGS AF: 0.954 AC: 3312 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	0.78
Dann	Benign	0.39

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

LitVar

Other links and lift over

dbSNP: rs2422862; hg19: chr20-3199703;