rs12032814

Positions:

• chr1-9247171-T-A
• chr1-9247171-T-C
• chr1-9247171-T-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_004285.4(H6PD):​c.745+88T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.221 in 899,800 control chromosomes in the GnomAD database, including 23,554 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.23 (4318 hom., cov: 32)
  • Exomes 𝑓: 0.22 (19236 hom.)
• Consequence: H6PD NM_004285.4 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.90

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 1-9247171-T-A is Benign according to our data. Variant chr1-9247171-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 191261.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.42 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
H6PD	NM_004285.4	c.745+88T>A		intron_variant		ENST00000377403.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
H6PD	ENST00000377403.7	c.745+88T>A		intron_variant		1	NM_004285.4	P1
H6PD	ENST00000602477.1	c.778+88T>A		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.234 AC: 35397 AN: 151302 Hom.: 4315 Cov.: 32

Gnomad AFR AF: 0.233

Gnomad AMI AF: 0.286

Gnomad AMR AF: 0.241

Gnomad ASJ AF: 0.172

Gnomad EAS AF: 0.435

Gnomad SAS AF: 0.169

Gnomad FIN AF: 0.153

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.237

Gnomad OTH AF: 0.241

GnomAD4 exome AF: 0.219 AC: 163630 AN: 748382 Hom.: 19236 AF XY: 0.216 AC XY: 86263 AN XY: 399254

Gnomad4 AFR exome AF: 0.227

Gnomad4 AMR exome AF: 0.238

Gnomad4 ASJ exome AF: 0.182

Gnomad4 EAS exome AF: 0.406

Gnomad4 SAS exome AF: 0.150

Gnomad4 FIN exome AF: 0.160

Gnomad4 NFE exome AF: 0.220

Gnomad4 OTH exome AF: 0.225

GnomAD4 genome AF: 0.234 AC: 35424 AN: 151418 Hom.: 4318 Cov.: 32 AF XY: 0.231 AC XY: 17069 AN XY: 73974

Gnomad4 AFR AF: 0.233

Gnomad4 AMR AF: 0.241

Gnomad4 ASJ AF: 0.172

Gnomad4 EAS AF: 0.435

Gnomad4 SAS AF: 0.169

Gnomad4 FIN AF: 0.153

Gnomad4 NFE AF: 0.237

Gnomad4 OTH AF: 0.239

Alfa AF: 0.216 Hom.: 478

Bravo AF: 0.245

Asia WGS AF: 0.251 AC: 871 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

research

Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center

Sep 28, 2016

- -

Cortisone reductase deficiency 1 Benign:1

Benign, criteria provided, single submitter

clinical testing

Mendelics

May 28, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.3
DANN	Benign	0.77

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: rs12032814; hg19: chr1-9307230; COSMIC: COSV66231125;