Variant rs41301427 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001395413.1(POR):c.1389+32G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.093 in 1,557,518 control chromosomes in the GnomAD database, including 7,427 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 0.074 ( 538 hom., cov: 33)

Exomes 𝑓: 0.095 ( 6889 hom. )

Consequence

POR
NM_001395413.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.457

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.133 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POR	NM_001395413.1 linkuse as main transcript	c.1389+32G>A		intron_variant		ENST00000461988.6	NP_001382342.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POR	ENST00000461988.6 linkuse as main transcript	c.1389+32G>A		intron_variant		1	NM_001395413.1	ENSP00000419970	P4

Frequencies

GnomAD3 genomes

AF:

0.0741

AC:

11284

AN:

152178

Hom.:

537

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0427

Gnomad AMI

AF:

0.305

Gnomad AMR

AF:

0.0586

Gnomad ASJ

AF:

0.0844

Gnomad EAS

AF:

0.0266

Gnomad SAS

AF:

0.142

Gnomad FIN

AF:

0.0442

Gnomad MID

AF:

0.104

Gnomad NFE

AF:

0.0962

Gnomad OTH

AF:

0.0842

GnomAD3 exomes

AF:

0.0850

AC:

16056

AN:

188896

Hom.:

774

AF XY:

0.0916

AC XY:

9568

AN XY:

104480

show subpopulations

Gnomad AFR exome

AF:

0.0416

Gnomad AMR exome

AF:

0.0463

Gnomad ASJ exome

AF:

0.0873

Gnomad EAS exome

AF:

0.0284

Gnomad SAS exome

AF:

0.155

Gnomad FIN exome

AF:

0.0544

Gnomad NFE exome

AF:

0.0980

Gnomad OTH exome

AF:

0.0828

GnomAD4 exome

AF:

0.0951

AC:

133606

AN:

1405222

Hom.:

6889

Cov.:

AF XY:

0.0971

AC XY:

67393

AN XY:

693800

show subpopulations

Gnomad4 AFR exome

AF:

0.0413

Gnomad4 AMR exome

AF:

0.0479

Gnomad4 ASJ exome

AF:

0.0873

Gnomad4 EAS exome

AF:

0.0183

Gnomad4 SAS exome

AF:

0.147

Gnomad4 FIN exome

AF:

0.0522

Gnomad4 NFE exome

AF:

0.0993

Gnomad4 OTH exome

AF:

0.0863

GnomAD4 genome

AF:

0.0742

AC:

11296

AN:

152296

Hom.:

538

Cov.:

AF XY:

0.0733

AC XY:

5458

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.0427

Gnomad4 AMR

AF:

0.0584

Gnomad4 ASJ

AF:

0.0844

Gnomad4 EAS

AF:

0.0267

Gnomad4 SAS

AF:

0.142

Gnomad4 FIN

AF:

0.0442

Gnomad4 NFE

AF:

0.0962

Gnomad4 OTH

AF:

0.0871

Alfa

AF:

0.0839

Hom.:

108

Bravo

AF:

0.0716

Asia WGS

AF:

0.0730

AC:

255

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

1.9

DANN

Benign

0.87

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over