rs7524046

chr1-9246974-G-Achr1-9246974-G-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.424

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]

ACMG classification

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	UniProt
H6PD	NM_004285.4	c.636G>A	p.Ala212=	synonymous_variant	3/5	ENST00000377403.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
H6PD	ENST00000377403.7	c.636G>A	p.Ala212=	synonymous_variant	3/5	1	NM_004285.4	P1
H6PD	ENST00000602477.1	c.669G>A	p.Ala223=	synonymous_variant	3/5	1

Frequencies

GnomAD3 genomes AF: 0.211 AC: 32048 AN: 151970 Hom.: 3678 Cov.: 31

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

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.: 31 AF XY: 0.236 AC XY: 171090 AN XY: 724012

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.: 31 AF XY: 0.208 AC XY: 15487 AN XY: 74350

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:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 18, 2020	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -

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

Other links and lift over

dbSNP: rs7524046; hg19: chr1-9307033; COSMIC: COSV66230512;