rs2071429

Positions:

• chrX-154532293-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001360016.2(G6PD):​c.1365-13C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.643 in 111,457 control chromosomes in the GnomAD database, including 19,987 homozygotes. There are 21,675 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.64 (19987 hom., 21675 hem., cov: 24)
  • Exomes 𝑓: 0.83 (260609 hom. 297468 hem.)
  • Failed GnomAD Quality Control
• Consequence: G6PD NM_001360016.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.817

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant X-154532293-G-A is Benign according to our data. Variant chrX-154532293-G-A is described in ClinVar as [Benign]. Clinvar id is 994337.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.856 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
G6PD	NM_001360016.2	c.1365-13C>T		intron_variant		ENST00000393562.10	NP_001346945.1
G6PD	NM_000402.4	c.1455-13C>T		intron_variant			NP_000393.4
G6PD	NM_001042351.3	c.1365-13C>T		intron_variant			NP_001035810.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
G6PD	ENST00000393562.10	c.1365-13C>T		intron_variant		1	NM_001360016.2	ENSP00000377192.3

Frequencies

GnomAD3 genomes AF: 0.643 AC: 71628 AN: 111406 Hom.: 19990 Cov.: 24 AF XY: 0.644 AC XY: 21656 AN XY: 33622

Gnomad AFR AF: 0.151

Gnomad AMI AF: 0.875

Gnomad AMR AF: 0.729

Gnomad ASJ AF: 0.768

Gnomad EAS AF: 0.869

Gnomad SAS AF: 0.528

Gnomad FIN AF: 0.921

Gnomad MID AF: 0.678

Gnomad NFE AF: 0.863

Gnomad OTH AF: 0.658

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.828 AC: 908053 AN: 1097128 Hom.: 260609 Cov.: 47 AF XY: 0.820 AC XY: 297468 AN XY: 362642

Gnomad4 AFR exome AF: 0.134

Gnomad4 AMR exome AF: 0.756

Gnomad4 ASJ exome AF: 0.762

Gnomad4 EAS exome AF: 0.889

Gnomad4 SAS exome AF: 0.569

Gnomad4 FIN exome AF: 0.916

Gnomad4 NFE exome AF: 0.868

Gnomad4 OTH exome AF: 0.777

GnomAD4 genome AF: 0.643 AC: 71633 AN: 111457 Hom.: 19987 Cov.: 24 AF XY: 0.643 AC XY: 21675 AN XY: 33683

Gnomad4 AFR AF: 0.151

Gnomad4 AMR AF: 0.729

Gnomad4 ASJ AF: 0.768

Gnomad4 EAS AF: 0.869

Gnomad4 SAS AF: 0.531

Gnomad4 FIN AF: 0.921

Gnomad4 NFE AF: 0.862

Gnomad4 OTH AF: 0.663

Alfa AF: 0.753 Hom.: 9514

Bravo AF: 0.619

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

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 64.3% in gnomAD (BA1) and previously interpreted as benign (BP6). -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Feb 18, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.28

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2071429; hg19: chrX-153760508;