rs2472393

Positions:

• chrX-154543081-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001360016.2(G6PD):​c.120+2955A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.646 in 111,337 control chromosomes in the GnomAD database, including 20,026 homozygotes. There are 21,919 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.65 (20026 hom., 21919 hem., cov: 23)
• Consequence: G6PD NM_001360016.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.40

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]

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant X-154543081-T-C is Benign according to our data. Variant chrX-154543081-T-C is described in ClinVar as [Benign]. Clinvar id is 1722713.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.857 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
G6PD	NM_001360016.2	c.120+2955A>G		intron_variant		ENST00000393562.10	NP_001346945.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
G6PD	ENST00000393562.10	c.120+2955A>G		intron_variant		1	NM_001360016.2	ENSP00000377192	P4

Frequencies

GnomAD3 genomes AF: 0.646 AC: 71934 AN: 111286 Hom.: 20029 Cov.: 23 AF XY: 0.654 AC XY: 21899 AN XY: 33468

Gnomad AFR AF: 0.154

Gnomad AMI AF: 0.878

Gnomad AMR AF: 0.732

Gnomad ASJ AF: 0.769

Gnomad EAS AF: 0.870

Gnomad SAS AF: 0.537

Gnomad FIN AF: 0.923

Gnomad MID AF: 0.681

Gnomad NFE AF: 0.864

Gnomad OTH AF: 0.656

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.646 AC: 71940 AN: 111337 Hom.: 20026 Cov.: 23 AF XY: 0.654 AC XY: 21919 AN XY: 33529

Gnomad4 AFR AF: 0.153

Gnomad4 AMR AF: 0.732

Gnomad4 ASJ AF: 0.769

Gnomad4 EAS AF: 0.871

Gnomad4 SAS AF: 0.540

Gnomad4 FIN AF: 0.923

Gnomad4 NFE AF: 0.864

Gnomad4 OTH AF: 0.660

Alfa AF: 0.811 Hom.: 33295

Bravo AF: 0.619

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Anemia, nonspherocytic hemolytic, due to G6PD deficiency Benign:1

Benign, criteria provided, single submitter

curation

Dunham Lab, University of Washington

Aug 12, 2022

Variant found at a frequency of over 32% in gnomAD (BA1). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.24
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2472393; hg19: chrX-153771296;