Variant 19-34399417-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000175.5(GPI):c.1398+82G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.788 in 1,592,794 control chromosomes in the GnomAD database, including 505,099 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.67 ( 37688 hom., cov: 32)

Exomes 𝑓: 0.80 ( 467411 hom. )

Consequence

GPI
NM_000175.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.12

Variant links:

Genes affected

GPI (HGNC:4458): (glucose-6-phosphate isomerase) This gene encodes a member of the glucose phosphate isomerase protein family. The encoded protein has been identified as a moonlighting protein based on its ability to perform mechanistically distinct functions. In the cytoplasm, the gene product functions as a glycolytic enzyme (glucose-6-phosphate isomerase) that interconverts glucose-6-phosphate and fructose-6-phosphate. Extracellularly, the encoded protein (also referred to as neuroleukin) functions as a neurotrophic factor that promotes survival of skeletal motor neurons and sensory neurons, and as a lymphokine that induces immunoglobulin secretion. The encoded protein is also referred to as autocrine motility factor based on an additional function as a tumor-secreted cytokine and angiogenic factor. Defects in this gene are the cause of nonspherocytic hemolytic anemia and a severe enzyme deficiency can be associated with hydrops fetalis, immediate neonatal death and neurological impairment. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2016]

GPI links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 19-34399417-G-A is Benign according to our data. Variant chr19-34399417-G-A is described in ClinVar as [Benign]. Clinvar id is 1237555.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.822 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPI	NM_000175.5 linkuse as main transcript	c.1398+82G>A		intron_variant		ENST00000356487.11	NP_000166.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPI	ENST00000356487.11 linkuse as main transcript	c.1398+82G>A		intron_variant		1	NM_000175.5	ENSP00000348877	P1	P06744-1

Frequencies

GnomAD3 genomes

AF:

0.672

AC:

102142

AN:

151990

Hom.:

37692

Cov.:

show subpopulations

Gnomad AFR

AF:

0.347

Gnomad AMI

AF:

0.746

Gnomad AMR

AF:

0.702

Gnomad ASJ

AF:

0.789

Gnomad EAS

AF:

0.800

Gnomad SAS

AF:

0.638

Gnomad FIN

AF:

0.797

Gnomad MID

AF:

0.734

Gnomad NFE

AF:

0.828

Gnomad OTH

AF:

0.706

GnomAD4 exome

AF:

0.800

AC:

1152682

AN:

1440686

Hom.:

467411

Cov.:

AF XY:

0.798

AC XY:

572591

AN XY:

717974

show subpopulations

Gnomad4 AFR exome

AF:

0.332

Gnomad4 AMR exome

AF:

0.697

Gnomad4 ASJ exome

AF:

0.775

Gnomad4 EAS exome

AF:

0.833

Gnomad4 SAS exome

AF:

0.642

Gnomad4 FIN exome

AF:

0.794

Gnomad4 NFE exome

AF:

0.833

Gnomad4 OTH exome

AF:

0.770

GnomAD4 genome

AF:

0.672

AC:

102150

AN:

152108

Hom.:

37688

Cov.:

AF XY:

0.669

AC XY:

49758

AN XY:

74364

show subpopulations

Gnomad4 AFR

AF:

0.347

Gnomad4 AMR

AF:

0.702

Gnomad4 ASJ

AF:

0.789

Gnomad4 EAS

AF:

0.800

Gnomad4 SAS

AF:

0.637

Gnomad4 FIN

AF:

0.797

Gnomad4 NFE

AF:

0.828

Gnomad4 OTH

AF:

0.706

Alfa

AF:

0.723

Hom.:

6178

Bravo

AF:

0.656

Asia WGS

AF:

0.680

AC:

2364

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.062

DANN

Benign

0.61

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over