Variant 1-9264512-T-C 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.2019T>C(p.Tyr673=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.399 in 1,612,808 control chromosomes in the GnomAD database, including 130,814 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.42 ( 13577 hom., cov: 33)

Exomes 𝑓: 0.40 ( 117237 hom. )

Consequence

H6PD
NM_004285.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -3.55

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.95).

BP6

Variant 1-9264512-T-C is Benign according to our data. Variant chr1-9264512-T-C is described in ClinVar as [Benign]. Clinvar id is 1540015.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-9264512-T-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-3.55 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.483 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
H6PD	NM_004285.4 linkuse as main transcript	c.2019T>C	p.Tyr673=	synonymous_variant	5/5	ENST00000377403.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
H6PD	ENST00000377403.7 linkuse as main transcript	c.2019T>C	p.Tyr673=	synonymous_variant	5/5	1	NM_004285.4	P1	O95479-1
H6PD	ENST00000602477.1 linkuse as main transcript	c.2052T>C	p.Tyr684=	synonymous_variant	5/5	1			O95479-2

Frequencies

GnomAD3 genomes

AF:

0.418

AC:

63544

AN:

151990

Hom.:

13564

Cov.:

show subpopulations

Gnomad AFR

AF:

0.489

Gnomad AMI

AF:

0.484

Gnomad AMR

AF:

0.441

Gnomad ASJ

AF:

0.428

Gnomad EAS

AF:

0.155

Gnomad SAS

AF:

0.491

Gnomad FIN

AF:

0.337

Gnomad MID

AF:

0.510

Gnomad NFE

AF:

0.396

Gnomad OTH

AF:

0.402

GnomAD3 exomes

AF:

0.412

AC:

102994

AN:

250056

Hom.:

22379

AF XY:

0.413

AC XY:

55947

AN XY:

135554

show subpopulations

Gnomad AFR exome

AF:

0.485

Gnomad AMR exome

AF:

0.526

Gnomad ASJ exome

AF:

0.421

Gnomad EAS exome

AF:

0.154

Gnomad SAS exome

AF:

0.500

Gnomad FIN exome

AF:

0.338

Gnomad NFE exome

AF:

0.398

Gnomad OTH exome

AF:

0.407

GnomAD4 exome

AF:

0.397

AC:

579938

AN:

1460700

Hom.:

117237

Cov.:

AF XY:

0.400

AC XY:

290567

AN XY:

726670

show subpopulations

Gnomad4 AFR exome

AF:

0.493

Gnomad4 AMR exome

AF:

0.515

Gnomad4 ASJ exome

AF:

0.422

Gnomad4 EAS exome

AF:

0.135

Gnomad4 SAS exome

AF:

0.500

Gnomad4 FIN exome

AF:

0.343

Gnomad4 NFE exome

AF:

0.392

Gnomad4 OTH exome

AF:

0.395

GnomAD4 genome

AF:

0.418

AC:

63590

AN:

152108

Hom.:

13577

Cov.:

AF XY:

0.417

AC XY:

31040

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.489

Gnomad4 AMR

AF:

0.442

Gnomad4 ASJ

AF:

0.428

Gnomad4 EAS

AF:

0.154

Gnomad4 SAS

AF:

0.492

Gnomad4 FIN

AF:

0.337

Gnomad4 NFE

AF:

0.396

Gnomad4 OTH

AF:

0.405

Alfa

AF:

0.407

Hom.:

15180

Bravo

AF:

0.425

Asia WGS

AF:

0.334

AC:

1164

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 29, 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

-0.95

CADD

Benign

0.085

DANN

Benign

0.26

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