rs12032814

Variant names:

• chr1-9247171-T-A
• rs12032814
• NM_004285.4:c.745+88T>A

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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:3
• Conservation: PhyloP100: -1.90
• Publications: 4 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 -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 Benign/Likely_benign. ClinVar VariationId 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.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	H6PD	NM_004285.4	MANE Select	c.745+88T>A		intron	N/A	NP_004276.2
	H6PD	NM_001282587.2		c.778+88T>A		intron	N/A	NP_001269516.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	H6PD	ENST00000377403.7	TSL:1 MANE Select	c.745+88T>A		intron	N/A	ENSP00000366620.2
	H6PD	ENST00000602477.1	TSL:1	c.778+88T>A		intron	N/A	ENSP00000473348.1

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

African (AFR) AF: 0.227 AC: 4498 AN: 19780

American (AMR) AF: 0.238 AC: 10144 AN: 42692

Ashkenazi Jewish (ASJ) AF: 0.182 AC: 3911 AN: 21524

East Asian (EAS) AF: 0.406 AC: 14519 AN: 35798

South Asian (SAS) AF: 0.150 AC: 10764 AN: 71638

European-Finnish (FIN) AF: 0.160 AC: 8159 AN: 51072

Middle Eastern (MID) AF: 0.206 AC: 832 AN: 4036

European-Non Finnish (NFE) AF: 0.220 AC: 102554 AN: 465134

Other (OTH) AF: 0.225 AC: 8249 AN: 36708

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

African (AFR) AF: 0.233 AC: 9581 AN: 41176

American (AMR) AF: 0.241 AC: 3666 AN: 15220

Ashkenazi Jewish (ASJ) AF: 0.172 AC: 598 AN: 3468

East Asian (EAS) AF: 0.435 AC: 2237 AN: 5142

South Asian (SAS) AF: 0.169 AC: 808 AN: 4774

European-Finnish (FIN) AF: 0.153 AC: 1601 AN: 10470

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.237 AC: 16105 AN: 67866

Other (OTH) AF: 0.239 AC: 502 AN: 2098

Alfa AF: 0.216 Hom.: 478

Bravo AF: 0.245

Asia WGS AF: 0.251 AC: 871 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.3
DANN	Benign	0.77
PhyloP100		-1.9
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: rs12032814; hg19: chr1-9307230; COSMIC: COSV66231125;