rs2268169

chr1-9261182-G-Achr1-9261182-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004285.4(H6PD):c.746-877G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.395 in 151,828 control chromosomes in the GnomAD database, including 13,082 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.40 (13082 hom., cov: 31)
• Consequence: H6PD NM_004285.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.46

Genes affected

H6PD (HGNC:4795): (hexose-6-phosphate dehydrogenase/glucose 1-dehydrogenase) There are 2 forms of glucose-6-phosphate dehydrogenase. G form is X-linked and H form, encoded by this gene, is autosomally linked. This H form shows activity with other hexose-6-phosphates, especially galactose-6-phosphate, whereas the G form is specific for glucose-6-phosphate. Both forms are present in most tissues, but H form is not found in red cells. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.531 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
H6PD	NM_004285.4	c.746-877G>A		intron_variant		ENST00000377403.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
H6PD	ENST00000377403.7	c.746-877G>A		intron_variant		1	NM_004285.4	P1
H6PD	ENST00000602477.1	c.779-877G>A		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.396 AC: 60009 AN: 151710 Hom.: 13078 Cov.: 31

Gnomad AFR AF: 0.198

Gnomad AMI AF: 0.672

Gnomad AMR AF: 0.471

Gnomad ASJ AF: 0.441

Gnomad EAS AF: 0.548

Gnomad SAS AF: 0.429

Gnomad FIN AF: 0.368

Gnomad MID AF: 0.544

Gnomad NFE AF: 0.481

Gnomad OTH AF: 0.448

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

GnomAD4 genome AF: 0.395 AC: 60021 AN: 151828 Hom.: 13082 Cov.: 31 AF XY: 0.393 AC XY: 29168 AN XY: 74184

Gnomad4 AFR AF: 0.197

Gnomad4 AMR AF: 0.472

Gnomad4 ASJ AF: 0.441

Gnomad4 EAS AF: 0.548

Gnomad4 SAS AF: 0.430

Gnomad4 FIN AF: 0.368

Gnomad4 NFE AF: 0.481

Gnomad4 OTH AF: 0.446

Alfa AF: 0.478 Hom.: 23480

Bravo AF: 0.398

Asia WGS AF: 0.442 AC: 1536 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	4.9
Dann	Benign	0.68

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

Other links and lift over

dbSNP: rs2268169; hg19: chr1-9321241; COSMIC: COSV66230698; COSMIC: COSV66230698;