rs2071931

chr1-9269230-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004285.4(H6PD):c.*4361C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.191 in 152,208 control chromosomes in the GnomAD database, including 2,844 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 0.19 (2840 hom., cov: 32)
  • Exomes 𝑓: 0.27 (4 hom.)
• Consequence: H6PD NM_004285.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.319

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.217 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
H6PD	NM_004285.4	c.*4361C>T		3_prime_UTR_variant	5/5	ENST00000377403.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
H6PD	ENST00000377403.7	c.*4361C>T		3_prime_UTR_variant	5/5	1	NM_004285.4	P1
H6PD	ENST00000495451.1	n.2508+1193C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.191 AC: 29036 AN: 152030 Hom.: 2838 Cov.: 32

Gnomad AFR AF: 0.154

Gnomad AMI AF: 0.159

Gnomad AMR AF: 0.175

Gnomad ASJ AF: 0.175

Gnomad EAS AF: 0.196

Gnomad SAS AF: 0.179

Gnomad FIN AF: 0.177

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.220

Gnomad OTH AF: 0.208

GnomAD4 exome AF: 0.267 AC: 16 AN: 60 Hom.: 4 Cov.: 0 AF XY: 0.300 AC XY: 12 AN XY: 40

Gnomad4 AMR exome AF: 0.00

Gnomad4 FIN exome AF: 0.250

Gnomad4 NFE exome AF: 0.300

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.191 AC: 29054 AN: 152148 Hom.: 2840 Cov.: 32 AF XY: 0.187 AC XY: 13938 AN XY: 74382

Gnomad4 AFR AF: 0.154

Gnomad4 AMR AF: 0.175

Gnomad4 ASJ AF: 0.175

Gnomad4 EAS AF: 0.197

Gnomad4 SAS AF: 0.178

Gnomad4 FIN AF: 0.177

Gnomad4 NFE AF: 0.220

Gnomad4 OTH AF: 0.206

Alfa AF: 0.209 Hom.: 2405

Bravo AF: 0.191

Asia WGS AF: 0.186 AC: 646 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	5.0
Dann	Benign	0.68

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: rs2071931; hg19: chr1-9329289; COSMIC: COSV66232492; COSMIC: COSV66232492;