rs9434743

chr1-9264611-A-G

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.2118A>G(p.Ser706=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.392 in 1,612,562 control chromosomes in the GnomAD database, including 126,373 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.42 (13572 hom., cov: 33)
  • Exomes 𝑓: 0.39 (112801 hom.)
• Consequence: H6PD NM_004285.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -3.27

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=-0.94).
• BP6: Variant 1-9264611-A-G is Benign according to our data. Variant chr1-9264611-A-G is described in ClinVar as [Benign]. Clinvar id is 1264396.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-9264611-A-G is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-3.27 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.492 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
H6PD	NM_004285.4	c.2118A>G	p.Ser706=	synonymous_variant	5/5	ENST00000377403.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
H6PD	ENST00000377403.7	c.2118A>G	p.Ser706=	synonymous_variant	5/5	1	NM_004285.4	P1
H6PD	ENST00000602477.1	c.2151A>G	p.Ser717=	synonymous_variant	5/5	1

Frequencies

GnomAD3 genomes AF: 0.417 AC: 63292 AN: 151878 Hom.: 13558 Cov.: 33

Gnomad AFR AF: 0.499

Gnomad AMI AF: 0.478

Gnomad AMR AF: 0.453

Gnomad ASJ AF: 0.407

Gnomad EAS AF: 0.142

Gnomad SAS AF: 0.485

Gnomad FIN AF: 0.335

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.387

Gnomad OTH AF: 0.402

GnomAD3 exomes AF: 0.406 AC: 101346 AN: 249376 Hom.: 21870 AF XY: 0.406 AC XY: 54968 AN XY: 135318

Gnomad AFR exome AF: 0.495

Gnomad AMR exome AF: 0.526

Gnomad ASJ exome AF: 0.404

Gnomad EAS exome AF: 0.139

Gnomad SAS exome AF: 0.496

Gnomad FIN exome AF: 0.337

Gnomad NFE exome AF: 0.390

Gnomad OTH exome AF: 0.399

GnomAD4 exome AF: 0.389 AC: 568460 AN: 1460566 Hom.: 112801 Cov.: 48 AF XY: 0.392 AC XY: 284813 AN XY: 726598

Gnomad4 AFR exome AF: 0.501

Gnomad4 AMR exome AF: 0.515

Gnomad4 ASJ exome AF: 0.404

Gnomad4 EAS exome AF: 0.128

Gnomad4 SAS exome AF: 0.495

Gnomad4 FIN exome AF: 0.341

Gnomad4 NFE exome AF: 0.383

Gnomad4 OTH exome AF: 0.388

GnomAD4 genome AF: 0.417 AC: 63337 AN: 151996 Hom.: 13572 Cov.: 33 AF XY: 0.416 AC XY: 30938 AN XY: 74300

Gnomad4 AFR AF: 0.498

Gnomad4 AMR AF: 0.453

Gnomad4 ASJ AF: 0.407

Gnomad4 EAS AF: 0.142

Gnomad4 SAS AF: 0.485

Gnomad4 FIN AF: 0.335

Gnomad4 NFE AF: 0.387

Gnomad4 OTH AF: 0.404

Alfa AF: 0.401 Hom.: 4376

Bravo AF: 0.424

Asia WGS AF: 0.318 AC: 1110 AN: 3478

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	Invitae	Jan 29, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 16, 2021	- -

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	-0.94
Cadd	Benign	0.081
Dann	Benign	0.34

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

Other links and lift over

dbSNP: rs9434743; hg19: chr1-9324670; COSMIC: COSV66230147; COSMIC: COSV66230147;