NM_001395413.1:c.180-6049A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001395413.1(POR):​c.180-6049A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.684 in 152,064 control chromosomes in the GnomAD database, including 35,754 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.68 ( 35754 hom., cov: 31)

Consequence

POR
NM_001395413.1 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.320

Publications

8 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

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.93).
BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.727 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PORNM_001395413.1 linkc.180-6049A>G intron_variant Intron 2 of 15 ENST00000461988.6 NP_001382342.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PORENST00000461988.6 linkc.180-6049A>G intron_variant Intron 2 of 15 1 NM_001395413.1 ENSP00000419970.2 P16435

Frequencies

GnomAD3 genomes
AF:
0.684
AC:
103898
AN:
151946
Hom.:
35735
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.678
Gnomad AMI
AF:
0.794
Gnomad AMR
AF:
0.675
Gnomad ASJ
AF:
0.574
Gnomad EAS
AF:
0.576
Gnomad SAS
AF:
0.749
Gnomad FIN
AF:
0.768
Gnomad MID
AF:
0.538
Gnomad NFE
AF:
0.685
Gnomad OTH
AF:
0.682
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.684
AC:
103957
AN:
152064
Hom.:
35754
Cov.:
31
AF XY:
0.690
AC XY:
51259
AN XY:
74338
show subpopulations
African (AFR)
AF:
0.677
AC:
28097
AN:
41472
American (AMR)
AF:
0.675
AC:
10322
AN:
15282
Ashkenazi Jewish (ASJ)
AF:
0.574
AC:
1991
AN:
3468
East Asian (EAS)
AF:
0.575
AC:
2957
AN:
5140
South Asian (SAS)
AF:
0.747
AC:
3603
AN:
4822
European-Finnish (FIN)
AF:
0.768
AC:
8143
AN:
10596
Middle Eastern (MID)
AF:
0.544
AC:
160
AN:
294
European-Non Finnish (NFE)
AF:
0.685
AC:
46531
AN:
67968
Other (OTH)
AF:
0.677
AC:
1429
AN:
2110
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.506
Heterozygous variant carriers
0
1712
3424
5137
6849
8561
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
824
1648
2472
3296
4120
<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:
0.673
Hom.:
42244
Bravo
AF:
0.667
Asia WGS
AF:
0.671
AC:
2333
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.93
CADD
Benign
3.7
DANN
Benign
0.41
PhyloP100
-0.32
Mutation Taster
=100/0
polymorphism (auto)

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs7804806; hg19: chr7-75595682; API