Variant rs12032814 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_004285.4(H6PD):c.745+88T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.221 in 899,800 control chromosomes in the GnomAD database, including 23,554 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.23 ( 4318 hom., cov: 32)

Exomes 𝑓: 0.22 ( 19236 hom. )

Consequence

H6PD
NM_004285.4 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.90

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 1-9247171-T-A is Benign according to our data. Variant chr1-9247171-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 191261.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.42 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
H6PD	NM_004285.4 linkuse as main transcript	c.745+88T>A		intron_variant		ENST00000377403.7	NP_004276.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
H6PD	ENST00000377403.7 linkuse as main transcript	c.745+88T>A		intron_variant		1	NM_004285.4	ENSP00000366620	P1	O95479-1
H6PD	ENST00000602477.1 linkuse as main transcript	c.778+88T>A		intron_variant		1		ENSP00000473348		O95479-2

Frequencies

GnomAD3 genomes

AF:

0.234

AC:

35397

AN:

151302

Hom.:

4315

Cov.:

show subpopulations

Gnomad AFR

AF:

0.233

Gnomad AMI

AF:

0.286

Gnomad AMR

AF:

0.241

Gnomad ASJ

AF:

0.172

Gnomad EAS

AF:

0.435

Gnomad SAS

AF:

0.169

Gnomad FIN

AF:

0.153

Gnomad MID

AF:

0.218

Gnomad NFE

AF:

0.237

Gnomad OTH

AF:

0.241

GnomAD4 exome

AF:

0.219

AC:

163630

AN:

748382

Hom.:

19236

AF XY:

0.216

AC XY:

86263

AN XY:

399254

show subpopulations

Gnomad4 AFR exome

AF:

0.227

Gnomad4 AMR exome

AF:

0.238

Gnomad4 ASJ exome

AF:

0.182

Gnomad4 EAS exome

AF:

0.406

Gnomad4 SAS exome

AF:

0.150

Gnomad4 FIN exome

AF:

0.160

Gnomad4 NFE exome

AF:

0.220

Gnomad4 OTH exome

AF:

0.225

GnomAD4 genome

AF:

0.234

AC:

35424

AN:

151418

Hom.:

4318

Cov.:

AF XY:

0.231

AC XY:

17069

AN XY:

73974

show subpopulations

Gnomad4 AFR

AF:

0.233

Gnomad4 AMR

AF:

0.241

Gnomad4 ASJ

AF:

0.172

Gnomad4 EAS

AF:

0.435

Gnomad4 SAS

AF:

0.169

Gnomad4 FIN

AF:

0.153

Gnomad4 NFE

AF:

0.237

Gnomad4 OTH

AF:

0.239

Alfa

AF:

0.216

Hom.:

478

Bravo

AF:

0.245

Asia WGS

AF:

0.251

AC:

871

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

research

Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center

Sep 28, 2016

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Cortisone reductase deficiency 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Mendelics

May 28, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

3.3

DANN

Benign

0.77

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over