Variant X-154545801-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBS1BS2_Supporting

The NM_001360016.2(G6PD):c.120+235G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.031 ( 64 hom., 694 hem., cov: 19)

Exomes 𝑓: 0.036 ( 170 hom. 2814 hem. )

Consequence

G6PD
NM_001360016.2 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.301

Variant links:

Genes affected

G6PD (HGNC:4057): (glucose-6-phosphate dehydrogenase) This gene encodes glucose-6-phosphate dehydrogenase. This protein is a cytosolic enzyme encoded by a housekeeping X-linked gene whose main function is to produce NADPH, a key electron donor in the defense against oxidizing agents and in reductive biosynthetic reactions. G6PD is remarkable for its genetic diversity. Many variants of G6PD, mostly produced from missense mutations, have been described with wide ranging levels of enzyme activity and associated clinical symptoms. G6PD deficiency may cause neonatal jaundice, acute hemolysis, or severe chronic non-spherocytic hemolytic anemia. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

G6PD links:

IKBKG (HGNC:5961): (inhibitor of nuclear factor kappa B kinase regulatory subunit gamma) This gene encodes the regulatory subunit of the inhibitor of kappaB kinase (IKK) complex, which activates NF-kappaB resulting in activation of genes involved in inflammation, immunity, cell survival, and other pathways. Mutations in this gene result in incontinentia pigmenti, hypohidrotic ectodermal dysplasia, and several other types of immunodeficiencies. A pseudogene highly similar to this locus is located in an adjacent region of the X chromosome. [provided by RefSeq, Mar 2016]

IKBKG links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BP6

Variant X-154545801-C-T is Benign according to our data. Variant chrX-154545801-C-T is described in ClinVar as [Benign]. Clinvar id is 1228119.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0307 (3230/105287) while in subpopulation NFE AF= 0.0491 (2497/50885). AF 95% confidence interval is 0.0475. There are 64 homozygotes in gnomad4. There are 694 alleles in male gnomad4 subpopulation. Median coverage is 19. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 64 XL geneVariant has number of homozygotes lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
G6PD	NM_001360016.2 linkuse as main transcript	c.120+235G>A		intron_variant		ENST00000393562.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
G6PD	ENST00000393562.10 linkuse as main transcript	c.120+235G>A		intron_variant		1	NM_001360016.2	P4	P11413-1

Frequencies

GnomAD3 genomes

AF:

0.0307

AC:

3228

AN:

105242

Hom.:

Cov.:

AF XY:

0.0248

AC XY:

693

AN XY:

27942

show subpopulations

Gnomad AFR

AF:

0.00599

Gnomad AMI

AF:

0.0359

Gnomad AMR

AF:

0.0124

Gnomad ASJ

AF:

0.0276

Gnomad EAS

AF:

0.000586

Gnomad SAS

AF:

0.0238

Gnomad FIN

AF:

0.0484

Gnomad MID

AF:

0.0173

Gnomad NFE

AF:

0.0490

Gnomad OTH

AF:

0.0180

GnomAD4 exome

AF:

0.0363

AC:

9319

AN:

256841

Hom.:

170

Cov.:

AF XY:

0.0365

AC XY:

2814

AN XY:

77127

show subpopulations

Gnomad4 AFR exome

AF:

0.00620

Gnomad4 AMR exome

AF:

0.00858

Gnomad4 ASJ exome

AF:

0.0179

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0296

Gnomad4 FIN exome

AF:

0.0485

Gnomad4 NFE exome

AF:

0.0447

Gnomad4 OTH exome

AF:

0.0340

GnomAD4 genome

AF:

0.0307

AC:

3230

AN:

105287

Hom.:

Cov.:

AF XY:

0.0248

AC XY:

694

AN XY:

27997

show subpopulations

Gnomad4 AFR

AF:

0.00598

Gnomad4 AMR

AF:

0.0124

Gnomad4 ASJ

AF:

0.0276

Gnomad4 EAS

AF:

0.000588

Gnomad4 SAS

AF:

0.0244

Gnomad4 FIN

AF:

0.0484

Gnomad4 NFE

AF:

0.0491

Gnomad4 OTH

AF:

0.0178

Alfa

AF:

0.0440

Hom.:

233

Bravo

AF:

0.0270

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

1.6

DANN

Benign

0.48

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