NM_004285.4:c.2118A>G

Variant names:

• chr1-9264611-A-G
• rs9434743
• NM_004285.4:c.2118A>G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -3.27
• Publications: 16 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 -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 VariationId is 1264396.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004285.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	H6PD	NM_004285.4	MANE Select	c.2118A>G	p.Ser706Ser	synonymous	Exon 5 of 5	NP_004276.2
	H6PD	NM_001282587.2		c.2151A>G	p.Ser717Ser	synonymous	Exon 5 of 5	NP_001269516.1	O95479-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	H6PD	ENST00000377403.7	TSL:1 MANE Select	c.2118A>G	p.Ser706Ser	synonymous	Exon 5 of 5	ENSP00000366620.2	O95479-1
	H6PD	ENST00000602477.1	TSL:1	c.2151A>G	p.Ser717Ser	synonymous	Exon 5 of 5	ENSP00000473348.1	O95479-2
	H6PD	ENST00000891474.1		c.2118A>G	p.Ser706Ser	synonymous	Exon 5 of 5	ENSP00000561533.1

Frequencies

GnomAD3 genomes AF: 0.417 AC: 63292 AN: 151878 Hom.: 13558 Cov.: 33

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

GnomAD2 exomes AF: 0.406 AC: 101346 AN: 249376 AF XY: 0.406

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 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.: 48 AF XY: 0.392 AC XY: 284813 AN XY: 726598

African (AFR) AF: 0.501 AC: 16771 AN: 33474

American (AMR) AF: 0.515 AC: 23036 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.404 AC: 10541 AN: 26122

East Asian (EAS) AF: 0.128 AC: 5089 AN: 39696

South Asian (SAS) AF: 0.495 AC: 42684 AN: 86244

European-Finnish (FIN) AF: 0.341 AC: 17894 AN: 52446

Middle Eastern (MID) AF: 0.521 AC: 3004 AN: 5764

European-Non Finnish (NFE) AF: 0.383 AC: 426042 AN: 1111734

Other (OTH) AF: 0.388 AC: 23399 AN: 60370

GnomAD4 genome AF: 0.417 AC: 63337 AN: 151996 Hom.: 13572 Cov.: 33 AF XY: 0.416 AC XY: 30938 AN XY: 74300

African (AFR) AF: 0.498 AC: 20652 AN: 41478

American (AMR) AF: 0.453 AC: 6932 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.407 AC: 1412 AN: 3466

East Asian (EAS) AF: 0.142 AC: 730 AN: 5148

South Asian (SAS) AF: 0.485 AC: 2333 AN: 4808

European-Finnish (FIN) AF: 0.335 AC: 3542 AN: 10566

Middle Eastern (MID) AF: 0.500 AC: 147 AN: 294

European-Non Finnish (NFE) AF: 0.387 AC: 26298 AN: 67918

Other (OTH) AF: 0.404 AC: 855 AN: 2116

Alfa AF: 0.402 Hom.: 4481

Bravo AF: 0.424

Asia WGS AF: 0.318 AC: 1110 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	Cortisone reductase deficiency 1 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.081
DANN	Benign	0.34
PhyloP100		-3.3
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: rs9434743; hg19: chr1-9324670; COSMIC: COSV66230147; COSMIC: COSV66230147;