NM_004285.4:c.746-4514C>T

Variant names:

• chr1-9257545-C-T
• rs6662509
• NM_004285.4:c.746-4514C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004285.4(H6PD):​c.746-4514C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.169 in 152,164 control chromosomes in the GnomAD database, including 2,303 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.17 (2303 hom., cov: 32)
• Consequence: H6PD NM_004285.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0990
• Publications: 14 publications found

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 Gene-Disease associations (from GenCC):

• cortisone reductase deficiency 1

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• cortisone reductase deficiency

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.229 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
H6PD	NM_004285.4	c.746-4514C>T		intron_variant	Intron 3 of 4	ENST00000377403.7	NP_004276.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
H6PD	ENST00000377403.7	c.746-4514C>T		intron_variant	Intron 3 of 4	1	NM_004285.4	ENSP00000366620.2
H6PD	ENST00000602477.1	c.779-4514C>T		intron_variant	Intron 3 of 4	1		ENSP00000473348.1

Frequencies

GnomAD3 genomes AF: 0.169 AC: 25677 AN: 152046 Hom.: 2294 Cov.: 32

Gnomad AFR AF: 0.190

Gnomad AMI AF: 0.196

Gnomad AMR AF: 0.235

Gnomad ASJ AF: 0.140

Gnomad EAS AF: 0.0828

Gnomad SAS AF: 0.167

Gnomad FIN AF: 0.186

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.147

Gnomad OTH AF: 0.160

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.169 AC: 25701 AN: 152164 Hom.: 2303 Cov.: 32 AF XY: 0.173 AC XY: 12883 AN XY: 74384

African (AFR) AF: 0.189 AC: 7861 AN: 41514

American (AMR) AF: 0.235 AC: 3596 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.140 AC: 486 AN: 3470

East Asian (EAS) AF: 0.0832 AC: 431 AN: 5182

South Asian (SAS) AF: 0.167 AC: 806 AN: 4816

European-Finnish (FIN) AF: 0.186 AC: 1963 AN: 10570

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.147 AC: 9983 AN: 68012

Other (OTH) AF: 0.165 AC: 348 AN: 2110

Alfa AF: 0.157 Hom.: 3378

Bravo AF: 0.174

Asia WGS AF: 0.140 AC: 490 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	7.1
DANN	Benign	0.82
PhyloP100		0.099
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6662509; hg19: chr1-9317604;