Variant rs7524046 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_004285.4(H6PD):c.636G>A(p.Ala212=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.236 in 1,606,590 control chromosomes in the GnomAD database, including 46,858 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.21 ( 3679 hom., cov: 31)

Exomes 𝑓: 0.24 ( 43179 hom. )

Consequence

H6PD
NM_004285.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.424

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.7).

BP6

Variant 1-9246974-G-A is Benign according to our data. Variant chr1-9246974-G-A is described in ClinVar as [Benign]. Clinvar id is 1269315.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.424 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.414 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.636G>A	p.Ala212=	synonymous_variant	3/5	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.636G>A	p.Ala212=	synonymous_variant	3/5	1	NM_004285.4	ENSP00000366620	P1	O95479-1
H6PD	ENST00000602477.1 linkuse as main transcript	c.669G>A	p.Ala223=	synonymous_variant	3/5	1		ENSP00000473348		O95479-2

Frequencies

GnomAD3 genomes

AF:

0.211

AC:

32048

AN:

151970

Hom.:

3678

Cov.:

show subpopulations

Gnomad AFR

AF:

0.155

Gnomad AMI

AF:

0.285

Gnomad AMR

AF:

0.231

Gnomad ASJ

AF:

0.172

Gnomad EAS

AF:

0.429

Gnomad SAS

AF:

0.166

Gnomad FIN

AF:

0.151

Gnomad MID

AF:

0.218

Gnomad NFE

AF:

0.237

Gnomad OTH

AF:

0.229

GnomAD3 exomes

AF:

0.226

AC:

56934

AN:

251388

Hom.:

7169

AF XY:

0.225

AC XY:

30528

AN XY:

135882

show subpopulations

Gnomad AFR exome

AF:

0.150

Gnomad AMR exome

AF:

0.233

Gnomad ASJ exome

AF:

0.183

Gnomad EAS exome

AF:

0.428

Gnomad SAS exome

AF:

0.150

Gnomad FIN exome

AF:

0.160

Gnomad NFE exome

AF:

0.240

Gnomad OTH exome

AF:

0.232

GnomAD4 exome

AF:

0.239

AC:

347434

AN:

1454502

Hom.:

43179

Cov.:

AF XY:

0.236

AC XY:

171090

AN XY:

724012

show subpopulations

Gnomad4 AFR exome

AF:

0.156

Gnomad4 AMR exome

AF:

0.236

Gnomad4 ASJ exome

AF:

0.183

Gnomad4 EAS exome

AF:

0.400

Gnomad4 SAS exome

AF:

0.152

Gnomad4 FIN exome

AF:

0.162

Gnomad4 NFE exome

AF:

0.248

Gnomad4 OTH exome

AF:

0.236

GnomAD4 genome

AF:

0.211

AC:

32058

AN:

152088

Hom.:

3679

Cov.:

AF XY:

0.208

AC XY:

15487

AN XY:

74350

show subpopulations

Gnomad4 AFR

AF:

0.155

Gnomad4 AMR

AF:

0.231

Gnomad4 ASJ

AF:

0.172

Gnomad4 EAS

AF:

0.429

Gnomad4 SAS

AF:

0.167

Gnomad4 FIN

AF:

0.151

Gnomad4 NFE

AF:

0.237

Gnomad4 OTH

AF:

0.227

Alfa

AF:

0.236

Hom.:

8687

Bravo

AF:

0.220

Asia WGS

AF:

0.245

AC:

851

AN:

3478

EpiCase

AF:

0.237

EpiControl

AF:

0.250

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 18, 2020	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Cortisone reductase deficiency 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Apr 11, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.70

CADD

Benign

0.68

DANN

Benign

0.70

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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