Variant rs17148944 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001395413.1(POR):c.228+88G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0924 in 1,270,272 control chromosomes in the GnomAD database, including 6,199 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.076 ( 572 hom., cov: 32)

Exomes 𝑓: 0.095 ( 5627 hom. )

Consequence

POR
NM_001395413.1 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.0350

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

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

BP6

Variant 7-75972549-G-A is Benign according to our data. Variant chr7-75972549-G-A is described in ClinVar as [Benign]. Clinvar id is 1264470.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.142 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
POR	NM_001395413.1 linkuse as main transcript	c.228+88G>A		intron_variant		ENST00000461988.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
POR	ENST00000461988.6 linkuse as main transcript	c.228+88G>A		intron_variant		1	NM_001395413.1	P4

Frequencies

GnomAD3 genomes

AF:

0.0759

AC:

11556

AN:

152198

Hom.:

571

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0439

Gnomad AMI

AF:

0.308

Gnomad AMR

AF:

0.0627

Gnomad ASJ

AF:

0.0937

Gnomad EAS

AF:

0.00424

Gnomad SAS

AF:

0.152

Gnomad FIN

AF:

0.0439

Gnomad MID

AF:

0.104

Gnomad NFE

AF:

0.0989

Gnomad OTH

AF:

0.0894

GnomAD3 exomes

AF:

0.0849

AC:

13324

AN:

156952

Hom.:

695

AF XY:

0.0918

AC XY:

7625

AN XY:

83078

show subpopulations

Gnomad AFR exome

AF:

0.0402

Gnomad AMR exome

AF:

0.0484

Gnomad ASJ exome

AF:

0.0947

Gnomad EAS exome

AF:

0.00318

Gnomad SAS exome

AF:

0.156

Gnomad FIN exome

AF:

0.0490

Gnomad NFE exome

AF:

0.101

Gnomad OTH exome

AF:

0.0925

GnomAD4 exome

AF:

0.0946

AC:

105789

AN:

1117956

Hom.:

5627

Cov.:

AF XY:

0.0975

AC XY:

54986

AN XY:

563828

show subpopulations

Gnomad4 AFR exome

AF:

0.0421

Gnomad4 AMR exome

AF:

0.0520

Gnomad4 ASJ exome

AF:

0.0966

Gnomad4 EAS exome

AF:

0.00159

Gnomad4 SAS exome

AF:

0.153

Gnomad4 FIN exome

AF:

0.0501

Gnomad4 NFE exome

AF:

0.0995

Gnomad4 OTH exome

AF:

0.0874

GnomAD4 genome

AF:

0.0759

AC:

11565

AN:

152316

Hom.:

572

Cov.:

AF XY:

0.0751

AC XY:

5597

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.0439

Gnomad4 AMR

AF:

0.0626

Gnomad4 ASJ

AF:

0.0937

Gnomad4 EAS

AF:

0.00405

Gnomad4 SAS

AF:

0.151

Gnomad4 FIN

AF:

0.0439

Gnomad4 NFE

AF:

0.0990

Gnomad4 OTH

AF:

0.0918

Alfa

AF:

0.0957

Hom.:

693

Bravo

AF:

0.0733

Asia WGS

AF:

0.0750

AC:

265

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 17, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

3.0

DANN

Benign

0.73

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over