rs2286822

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001395413.1(POR):c.1239+12C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.301 in 1,578,350 control chromosomes in the GnomAD database, including 73,310 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.28 ( 6219 hom., cov: 32)

Exomes 𝑓: 0.30 ( 67091 hom. )

Consequence

POR
NM_001395413.1 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: -2.31

Publications

15 publications found

Variant links:

Genes affected

POR (HGNC:9208): (cytochrome p450 oxidoreductase) This gene encodes an endoplasmic reticulum membrane oxidoreductase that is essential for multiple metabolic processes, including reactions catalyzed by cytochrome P450 proteins for metabolism of steroid hormones, drugs and xenobiotics. The encoded protein has a flavin adenine dinucleotide (FAD)-binding domain and a flavodoxin-like domain which bind two cofactors, FAD and FMN, that allow it to donate electrons directly from NADPH to all microsomal P450 enzymes. Mutations in this gene cause a complex set of disorders, including apparent combined P450C17 and P450C21 deficiency, amenorrhea and disordered steroidogenesis, congenital adrenal hyperplasia and Antley-Bixler syndrome, that resemble those caused by defects in steroid metabolizing enzymes such as aromatase, 21-hydroxylase, and 17 alpha-hydroxylase. [provided by RefSeq, Aug 2020]

POR Gene-Disease associations (from GenCC):

Antley-Bixler syndrome with genital anomalies and disordered steroidogenesis
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: ClinGen, PanelApp Australia, Ambry Genetics
congenital adrenal hyperplasia due to cytochrome P450 oxidoreductase deficiency
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet
Antley-Bixler syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

POR links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BP6

Variant 7-75984970-C-T is Benign according to our data. Variant chr7-75984970-C-T is described in ClinVar as Benign. ClinVar VariationId is 256838.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.408 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POR	NM_001395413.1 link	c.1239+12C>T		intron_variant	Intron 11 of 15	ENST00000461988.6	NP_001382342.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POR	ENST00000461988.6 link	c.1239+12C>T		intron_variant	Intron 11 of 15	1	NM_001395413.1	ENSP00000419970.2		P16435

Frequencies

GnomAD3 genomes

AF:

0.281

AC:

42649

AN:

151510

Hom.:

6210

Cov.:

show subpopulations

Gnomad AFR

AF:

0.222

Gnomad AMI

AF:

0.238

Gnomad AMR

AF:

0.308

Gnomad ASJ

AF:

0.438

Gnomad EAS

AF:

0.423

Gnomad SAS

AF:

0.240

Gnomad FIN

AF:

0.237

Gnomad MID

AF:

0.443

Gnomad NFE

AF:

0.302

Gnomad OTH

AF:

0.291

GnomAD2 exomes

AF:

0.312

AC:

69624

AN:

223478

AF XY:

0.307

show subpopulations

Gnomad AFR exome

AF:

0.220

Gnomad AMR exome

AF:

0.364

Gnomad ASJ exome

AF:

0.430

Gnomad EAS exome

AF:

0.432

Gnomad FIN exome

AF:

0.238

Gnomad NFE exome

AF:

0.305

Gnomad OTH exome

AF:

0.317

GnomAD4 exome

AF:

0.303

AC:

432065

AN:

1426722

Hom.:

67091

Cov.:

AF XY:

0.302

AC XY:

213041

AN XY:

705662

show subpopulations

African (AFR)

AF:

0.220

AC:

7302

AN:

33128

American (AMR)

AF:

0.361

AC:

15705

AN:

43480

Ashkenazi Jewish (ASJ)

AF:

0.433

AC:

10520

AN:

24288

East Asian (EAS)

AF:

0.416

AC:

16192

AN:

38904

South Asian (SAS)

AF:

0.249

AC:

20606

AN:

82726

European-Finnish (FIN)

AF:

0.232

AC:

10825

AN:

46656

Middle Eastern (MID)

AF:

0.363

AC:

2032

AN:

5596

European-Non Finnish (NFE)

AF:

0.302

AC:

330358

AN:

1093048

Other (OTH)

AF:

0.315

AC:

18525

AN:

58896

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

16985

33970

50956

67941

84926

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11062

22124

33186

44248

55310

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.282

AC:

42687

AN:

151628

Hom.:

6219

Cov.:

AF XY:

0.278

AC XY:

20587

AN XY:

74128

show subpopulations

African (AFR)

AF:

0.222

AC:

9200

AN:

41422

American (AMR)

AF:

0.308

AC:

4698

AN:

15242

Ashkenazi Jewish (ASJ)

AF:

0.438

AC:

1511

AN:

3446

East Asian (EAS)

AF:

0.423

AC:

2159

AN:

5100

South Asian (SAS)

AF:

0.242

AC:

1158

AN:

4794

European-Finnish (FIN)

AF:

0.237

AC:

2508

AN:

10578

Middle Eastern (MID)

AF:

0.452

AC:

132

AN:

292

European-Non Finnish (NFE)

AF:

0.302

AC:

20484

AN:

67748

Other (OTH)

AF:

0.296

AC:

620

AN:

2096

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1565

3129

4694

6258

7823

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

446

892

1338

1784

2230

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.287

Hom.:

600

Bravo

AF:

0.293

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Feb 08, 2025

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Congenital adrenal hyperplasia due to cytochrome P450 oxidoreductase deficiency

Benign:2

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Antley-Bixler syndrome with genital anomalies and disordered steroidogenesis

Benign:1

Oct 25, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency

Benign:1

Pecori Giraldi Lab, University of Milan

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:case-control

This variant is intronic -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.014

(source)

DANN

Benign

0.72

PhyloP100

-2.3

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over