rs72557947

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001382655.3(POR):c.1498G>A(p.Ala500Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000489 in 1,593,634 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. A500A) has been classified as Benign.

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., cov: 36)

Exomes 𝑓: 0.000046 ( 0 hom. )

Consequence

POR
NM_001382655.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 0.388

Publications

6 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: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.020320505).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001382655.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
POR	NM_001395413.1	MANE Select	c.1444G>A	p.Ala482Thr	missense	Exon 13 of 16	NP_001382342.1
POR	NM_001382655.3		c.1498G>A	p.Ala500Thr	missense	Exon 14 of 17	NP_001369584.2
POR	NM_001367562.3		c.1444G>A	p.Ala482Thr	missense	Exon 14 of 17	NP_001354491.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
POR	ENST00000461988.6	TSL:1 MANE Select	c.1444G>A	p.Ala482Thr	missense	Exon 13 of 16	ENSP00000419970.2
POR	ENST00000447222.5	TSL:5	c.1603G>A	p.Ala535Thr	missense	Exon 12 of 15	ENSP00000393527.1
POR	ENST00000910548.1		c.1444G>A	p.Ala482Thr	missense	Exon 13 of 16	ENSP00000580607.1

Frequencies

GnomAD3 genomes

AF:

0.0000788

AC:

AN:

152254

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00231

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000104

AC:

AN:

221010

AF XY:

0.0000912

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00131

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000465

AC:

AN:

1441262

Hom.:

Cov.:

AF XY:

0.0000504

AC XY:

AN XY:

714606

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33168

American (AMR)

AF:

0.00

AC:

AN:

42868

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25288

East Asian (EAS)

AF:

0.00136

AC:

AN:

39006

South Asian (SAS)

AF:

0.0000843

AC:

AN:

83006

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50528

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5710

European-Non Finnish (NFE)

AF:

0.00000454

AC:

AN:

1102144

Other (OTH)

AF:

0.0000336

AC:

AN:

59544

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.0000722

AC:

AN:

152372

Hom.:

Cov.:

AF XY:

0.0000805

AC XY:

AN XY:

74508

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41592

American (AMR)

AF:

0.00

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00212

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68038

Other (OTH)

AF:

0.00

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00

Hom.:

Bravo

AF:

0.000113

ExAC

AF:

0.0000672

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Congenital adrenal hyperplasia due to cytochrome P450 oxidoreductase deficiency (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.064

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.48

CADD

Benign

0.64

(source)

DANN

Benign

0.90

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.36

LIST_S2

Benign

0.83

M_CAP

Benign

0.0082

MetaRNN

Benign

0.020

MetaSVM

Benign

-0.95

PhyloP100

0.39

PrimateAI

Benign

0.37

PROVEAN

Benign

2.7

REVEL

Benign

0.080

Sift

Benign

1.0

Sift4G

Benign

1.0

Vest4

0.045

MVP

0.22

MPC

0.11

ClinPred

0.016

GERP RS

-4.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

gMVP

0.20

Mutation Taster

=76/24

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over