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_004285.4(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_004285.4 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
H6PD	NM_004285.4 link	c.*4361C>T		3_prime_UTR_variant	Exon 5 of 5	ENST00000377403.7	NP_004276.2	O95479-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
H6PD	ENST00000377403.7 link	c.*4361C>T		3_prime_UTR_variant	Exon 5 of 5	1	NM_004285.4	ENSP00000366620.2		O95479-1
H6PD	ENST00000495451.1 link	n.2508+1193C>T		intron_variant	Intron 1 of 1	2

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 v4.3

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over