rs1135612

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_001395413.1(POR):c.378A>G(p.Pro126Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.254 in 1,612,602 control chromosomes in the GnomAD database, including 55,513 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.22 ( 4339 hom., cov: 32)

Exomes 𝑓: 0.26 ( 51174 hom. )

Consequence

POR
NM_001395413.1 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: -5.05

Publications

29 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 -19 ACMG points.

BP4

Computational evidence support a benign effect (REVEL=0.167).

BP6

Variant 7-75980359-A-G is Benign according to our data. Variant chr7-75980359-A-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 256842.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-5.05 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.443 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POR	NM_001395413.1 link	c.378A>G	p.Pro126Pro	synonymous_variant	Exon 5 of 16	ENST00000461988.6	NP_001382342.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POR	ENST00000461988.6 link	c.378A>G	p.Pro126Pro	synonymous_variant	Exon 5 of 16	1	NM_001395413.1	ENSP00000419970.2		P16435

Frequencies

GnomAD3 genomes

AF:

0.216

AC:

32884

AN:

152028

Hom.:

4332

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0776

Gnomad AMI

AF:

0.168

Gnomad AMR

AF:

0.319

Gnomad ASJ

AF:

0.319

Gnomad EAS

AF:

0.458

Gnomad SAS

AF:

0.209

Gnomad FIN

AF:

0.210

Gnomad MID

AF:

0.357

Gnomad NFE

AF:

0.255

Gnomad OTH

AF:

0.234

GnomAD2 exomes

AF:

0.276

AC:

68491

AN:

248368

AF XY:

0.269

show subpopulations

Gnomad AFR exome

AF:

0.0721

Gnomad AMR exome

AF:

0.421

Gnomad ASJ exome

AF:

0.313

Gnomad EAS exome

AF:

0.470

Gnomad FIN exome

AF:

0.212

Gnomad NFE exome

AF:

0.256

Gnomad OTH exome

AF:

0.271

GnomAD4 exome

AF:

0.257

AC:

375938

AN:

1460456

Hom.:

51174

Cov.:

AF XY:

0.256

AC XY:

186175

AN XY:

726410

show subpopulations

African (AFR)

AF:

0.0706

AC:

2364

AN:

33474

American (AMR)

AF:

0.405

AC:

18114

AN:

44692

Ashkenazi Jewish (ASJ)

AF:

0.315

AC:

8234

AN:

26130

East Asian (EAS)

AF:

0.457

AC:

18142

AN:

39682

South Asian (SAS)

AF:

0.209

AC:

18067

AN:

86248

European-Finnish (FIN)

AF:

0.209

AC:

11007

AN:

52544

Middle Eastern (MID)

AF:

0.273

AC:

1571

AN:

5764

European-Non Finnish (NFE)

AF:

0.254

AC:

282837

AN:

1111568

Other (OTH)

AF:

0.259

AC:

15602

AN:

60354

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

16521

33042

49562

66083

82604

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9636

19272

28908

38544

48180

<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:

0.216

AC:

32906

AN:

152146

Hom.:

4339

Cov.:

AF XY:

0.216

AC XY:

16082

AN XY:

74378

show subpopulations

African (AFR)

AF:

0.0774

AC:

3216

AN:

41542

American (AMR)

AF:

0.319

AC:

4876

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.319

AC:

1107

AN:

3468

East Asian (EAS)

AF:

0.458

AC:

2351

AN:

5134

South Asian (SAS)

AF:

0.210

AC:

1014

AN:

4822

European-Finnish (FIN)

AF:

0.210

AC:

2223

AN:

10600

Middle Eastern (MID)

AF:

0.366

AC:

107

AN:

292

European-Non Finnish (NFE)

AF:

0.255

AC:

17353

AN:

67976

Other (OTH)

AF:

0.239

AC:

506

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1271

2543

3814

5086

6357

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

352

704

1056

1408

1760

<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:

0.252

Hom.:

15929

Bravo

AF:

0.225

Asia WGS

AF:

0.322

AC:

1116

AN:

3478

EpiCase

AF:

0.264

EpiControl

AF:

0.254

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

Significance:Benign

Review Status:no assertion criteria provided

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 13, 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

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

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:Likely benign

Review Status:criteria provided, single submitter

Collection Method:case-control

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.040

(source)

DANN

Benign

0.37

PhyloP100

-5.1

Mutation Taster

=290/10

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