rs6688832

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_004285.4(H6PD):c.1358G>A(p.Arg453Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.254 in 1,613,468 control chromosomes in the GnomAD database, including 55,605 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.31 ( 8155 hom., cov: 33)

Exomes 𝑓: 0.25 ( 47450 hom. )

Consequence

H6PD
NM_004285.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts U:1B:3

Conservation

PhyloP100: -0.0830

Publications

52 publications found

Variant links:

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

H6PD links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=5.1385164E-4).

BP6

Variant 1-9263851-G-A is Benign according to our data. Variant chr1-9263851-G-A is described in ClinVar as Benign. ClinVar VariationId is 16131.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.455 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	H6PD	NM_004285.4	MANE Select	c.1358G>A	p.Arg453Gln	missense	Exon 5 of 5	NP_004276.2
	H6PD	NM_001282587.2		c.1391G>A	p.Arg464Gln	missense	Exon 5 of 5	NP_001269516.1	O95479-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
H6PD	ENST00000377403.7	TSL:1 MANE Select	c.1358G>A	p.Arg453Gln	missense	Exon 5 of 5	ENSP00000366620.2	O95479-1
H6PD	ENST00000602477.1	TSL:1	c.1391G>A	p.Arg464Gln	missense	Exon 5 of 5	ENSP00000473348.1	O95479-2
H6PD	ENST00000891474.1		c.1358G>A	p.Arg453Gln	missense	Exon 5 of 5	ENSP00000561533.1

Frequencies

GnomAD3 genomes

AF:

0.312

AC:

47384

AN:

152016

Hom.:

8121

Cov.:

show subpopulations

Gnomad AFR

AF:

0.458

Gnomad AMI

AF:

0.238

Gnomad AMR

AF:

0.317

Gnomad ASJ

AF:

0.263

Gnomad EAS

AF:

0.471

Gnomad SAS

AF:

0.294

Gnomad FIN

AF:

0.220

Gnomad MID

AF:

0.215

Gnomad NFE

AF:

0.229

Gnomad OTH

AF:

0.303

GnomAD2 exomes

AF:

0.284

AC:

71377

AN:

250914

AF XY:

0.277

show subpopulations

Gnomad AFR exome

AF:

0.464

Gnomad AMR exome

AF:

0.333

Gnomad ASJ exome

AF:

0.277

Gnomad EAS exome

AF:

0.472

Gnomad FIN exome

AF:

0.219

Gnomad NFE exome

AF:

0.229

Gnomad OTH exome

AF:

0.264

GnomAD4 exome

AF:

0.248

AC:

362167

AN:

1461334

Hom.:

47450

Cov.:

AF XY:

0.248

AC XY:

180035

AN XY:

727004

show subpopulations

African (AFR)

AF:

0.463

AC:

15489

AN:

33474

American (AMR)

AF:

0.333

AC:

14885

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.282

AC:

7379

AN:

26132

East Asian (EAS)

AF:

0.467

AC:

18553

AN:

39700

South Asian (SAS)

AF:

0.276

AC:

23825

AN:

86256

European-Finnish (FIN)

AF:

0.219

AC:

11639

AN:

53196

Middle Eastern (MID)

AF:

0.251

AC:

1446

AN:

5768

European-Non Finnish (NFE)

AF:

0.228

AC:

252981

AN:

1111700

Other (OTH)

AF:

0.264

AC:

15970

AN:

60384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

18034

36068

54103

72137

90171

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9012

18024

27036

36048

45060

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.312

AC:

47458

AN:

152134

Hom.:

8155

Cov.:

AF XY:

0.311

AC XY:

23157

AN XY:

74388

show subpopulations

African (AFR)

AF:

0.458

AC:

19035

AN:

41518

American (AMR)

AF:

0.317

AC:

4842

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.263

AC:

912

AN:

3468

East Asian (EAS)

AF:

0.470

AC:

2424

AN:

5154

South Asian (SAS)

AF:

0.293

AC:

1413

AN:

4826

European-Finnish (FIN)

AF:

0.220

AC:

2328

AN:

10594

Middle Eastern (MID)

AF:

0.214

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.229

AC:

15586

AN:

67972

Other (OTH)

AF:

0.303

AC:

639

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1644

3289

4933

6578

8222

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

462

924

1386

1848

2310

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.251

Hom.:

12962

Bravo

AF:

0.324

TwinsUK

AF:

0.231

AC:

858

ALSPAC

AF:

0.242

AC:

932

ESP6500AA

AF:

0.458

AC:

2017

ESP6500EA

AF:

0.229

AC:

1971

ExAC

AF:

0.284

AC:

34526

Asia WGS

AF:

0.406

AC:

1409

AN:

3478

EpiCase

AF:

0.235

EpiControl

AF:

0.240

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

Cortisone reductase deficiency 1 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.29

CADD

Benign

2.2

(source)

DANN

Benign

0.67

DEOGEN2

Benign

0.39

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.050

LIST_S2

Benign

0.13

MetaRNN

Benign

0.00051

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.7

PhyloP100

-0.083

PrimateAI

Benign

0.20

PROVEAN

Benign

0.48

REVEL

Benign

0.18

Sift

Benign

0.57

Sift4G

Benign

0.57

Polyphen

0.0010

Vest4

0.049

MPC

0.12

ClinPred

0.00059

GERP RS

-2.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.017

gMVP

0.36

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over