rs2071429

Variant names:

• chrX-154532293-G-A
• rs2071429
• NM_001360016.2:c.1365-13C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 33 publications found

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 Gene-Disease associations (from GenCC):

• anemia, nonspherocytic hemolytic, due to G6PD deficiency

  Inheritance: XL Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• G6PD deficiency

  Inheritance: XL Classification: DEFINITIVE Submitted by: ClinGen
• class I glucose-6-phosphate dehydrogenase deficiency

  Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
G6PD	NM_001360016.2	c.1365-13C>T		intron_variant	Intron 11 of 12	ENST00000393562.10	NP_001346945.1
G6PD	NM_000402.4	c.1455-13C>T		intron_variant	Intron 11 of 12		NP_000393.4
G6PD	NM_001042351.3	c.1365-13C>T		intron_variant	Intron 11 of 12		NP_001035810.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
G6PD	ENST00000393562.10	c.1365-13C>T		intron_variant	Intron 11 of 12	1	NM_001360016.2	ENSP00000377192.3

Frequencies

GnomAD3 genomes AF: 0.643 AC: 71628 AN: 111406 Hom.: 19990 Cov.: 24

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

African (AFR) AF: 0.134 AC: 3531 AN: 26388

American (AMR) AF: 0.756 AC: 26492 AN: 35034

Ashkenazi Jewish (ASJ) AF: 0.762 AC: 14759 AN: 19373

East Asian (EAS) AF: 0.889 AC: 26817 AN: 30182

South Asian (SAS) AF: 0.569 AC: 30759 AN: 54074

European-Finnish (FIN) AF: 0.916 AC: 36918 AN: 40299

Middle Eastern (MID) AF: 0.605 AC: 2493 AN: 4122

European-Non Finnish (NFE) AF: 0.868 AC: 730499 AN: 841592

Other (OTH) AF: 0.777 AC: 35785 AN: 46064

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

African (AFR) AF: 0.151 AC: 4669 AN: 30900

American (AMR) AF: 0.729 AC: 7705 AN: 10573

Ashkenazi Jewish (ASJ) AF: 0.768 AC: 2029 AN: 2642

East Asian (EAS) AF: 0.869 AC: 3031 AN: 3489

South Asian (SAS) AF: 0.531 AC: 1430 AN: 2693

European-Finnish (FIN) AF: 0.921 AC: 5513 AN: 5986

Middle Eastern (MID) AF: 0.692 AC: 146 AN: 211

European-Non Finnish (NFE) AF: 0.862 AC: 45518 AN: 52775

Other (OTH) AF: 0.663 AC: 1006 AN: 1518

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

Aug 12, 2022

Dunham Lab, University of Washington

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: curation

Variant found at a frequency of 64.3% in gnomAD (BA1) and previously interpreted as benign (BP6). -

not provided Benign:1

Feb 18, 2022

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.28
PhyloP100		-0.82

Splicing

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

Other links and lift over

dbSNP: rs2071429; hg19: chrX-153760508;