dbSNP rs2071931: H6PD:c.*4361C>T (chr1-9269230-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001282587.2(H6PD):c.*4361C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.191 in 152,208 control chromosomes in the GnomAD database, including 2,844 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 0.19 ( 2840 hom., cov: 32)

Exomes 𝑓: 0.27 ( 4 hom. )

Consequence

H6PD
NM_001282587.2 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.319

Publications

15 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.217 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001282587.2. 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.*4361C>T		3_prime_UTR	Exon 5 of 5	NP_004276.2
	H6PD	NM_001282587.2		c.*4361C>T		3_prime_UTR	Exon 5 of 5	NP_001269516.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	H6PD	ENST00000377403.7	TSL:1 MANE Select	c.*4361C>T		3_prime_UTR	Exon 5 of 5	ENSP00000366620.2
	H6PD	ENST00000495451.1	TSL:2	n.2508+1193C>T		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.191

AC:

29036

AN:

152030

Hom.:

2838

Cov.:

show subpopulations

Gnomad AFR

AF:

0.154

Gnomad AMI

AF:

0.159

Gnomad AMR

AF:

0.175

Gnomad ASJ

AF:

0.175

Gnomad EAS

AF:

0.196

Gnomad SAS

AF:

0.179

Gnomad FIN

AF:

0.177

Gnomad MID

AF:

0.244

Gnomad NFE

AF:

0.220

Gnomad OTH

AF:

0.208

GnomAD4 exome

AF:

0.267

AC:

AN:

Hom.:

Cov.:

AF XY:

0.300

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.250

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.300

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.191

AC:

29054

AN:

152148

Hom.:

2840

Cov.:

AF XY:

0.187

AC XY:

13938

AN XY:

74382

show subpopulations

African (AFR)

AF:

0.154

AC:

6386

AN:

41504

American (AMR)

AF:

0.175

AC:

2674

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.175

AC:

607

AN:

3470

East Asian (EAS)

AF:

0.197

AC:

1016

AN:

5166

South Asian (SAS)

AF:

0.178

AC:

860

AN:

4822

European-Finnish (FIN)

AF:

0.177

AC:

1873

AN:

10588

Middle Eastern (MID)

AF:

0.248

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.220

AC:

14987

AN:

67996

Other (OTH)

AF:

0.206

AC:

434

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1231

2462

3692

4923

6154

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

324

648

972

1296

1620

<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:

0.208

Hom.:

3368

Bravo

AF:

0.191

Asia WGS

AF:

0.186

AC:

646

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

5.0

(source)

DANN

Benign

0.68

PhyloP100

-0.32

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

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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