NM_004285.4:c.746-877G>A

Variant names:

• chr1-9261182-G-A
• rs2268169
• NM_004285.4:c.746-877G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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]

H6PD Gene-Disease associations (from GenCC):

• cortisone reductase deficiency 1

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• cortisone reductase deficiency

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004285.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	H6PD	NM_004285.4	MANE Select	c.746-877G>A		intron	N/A	NP_004276.2
	H6PD	NM_001282587.2		c.779-877G>A		intron	N/A	NP_001269516.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	H6PD	ENST00000377403.7	TSL:1 MANE Select	c.746-877G>A		intron	N/A	ENSP00000366620.2
	H6PD	ENST00000602477.1	TSL:1	c.779-877G>A		intron	N/A	ENSP00000473348.1

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

African (AFR) AF: 0.197 AC: 8173 AN: 41402

American (AMR) AF: 0.472 AC: 7193 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.441 AC: 1529 AN: 3470

East Asian (EAS) AF: 0.548 AC: 2815 AN: 5136

South Asian (SAS) AF: 0.430 AC: 2057 AN: 4788

European-Finnish (FIN) AF: 0.368 AC: 3877 AN: 10542

Middle Eastern (MID) AF: 0.541 AC: 159 AN: 294

European-Non Finnish (NFE) AF: 0.481 AC: 32672 AN: 67934

Other (OTH) AF: 0.446 AC: 937 AN: 2102

Alfa AF: 0.472 Hom.: 30307

Bravo AF: 0.398

Asia WGS AF: 0.442 AC: 1536 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	4.9
DANN	Benign	0.68
PhyloP100		1.5
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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