dbSNP rs9434743: H6PD:p.Ser706Ser (chr1-9264611-A-G) – ACMG Classification: Benign (-21 pts)

Variant summary

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

The NM_004285.4(H6PD):c.2118A>G(p.Ser706Ser) 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

Scores

Clinical Significance

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

Conservation

PhyloP100: -3.27

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=-0.94).

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 rank	MANE	Protein	UniProt
H6PD	NM_004285.4 link	c.2118A>G	p.Ser706Ser	synonymous_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.2118A>G	p.Ser706Ser	synonymous_variant	Exon 5 of 5	1	NM_004285.4	ENSP00000366620.2		O95479-1
H6PD	ENST00000602477.1 link	c.2151A>G	p.Ser717Ser	synonymous_variant	Exon 5 of 5	1		ENSP00000473348.1		O95479-2

Frequencies

GnomAD3 genomes

AF:

0.417

AC:

63292

AN:

151878

Hom.:

13558

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.392

AC XY:

284813

AN XY:

726598

show subpopulations

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.:

AF XY:

0.416

AC XY:

30938

AN XY:

74300

show subpopulations

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:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Mar 16, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Cortisone reductase deficiency 1

Benign:1

Apr 11, 2023

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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

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