Variant rs10239977 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.357+89C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.319 in 1,540,602 control chromosomes in the GnomAD database, including 83,573 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.27 ( 6166 hom., cov: 33)

Exomes 𝑓: 0.33 ( 77407 hom. )

Consequence

POR
NM_001395413.1 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.87

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=-0.92).

BP6

Variant 7-75979668-C-T is Benign according to our data. Variant chr7-75979668-C-T is described in ClinVar as [Benign]. Clinvar id is 1274770.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.352 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POR	NM_001395413.1 link	c.357+89C>T		intron_variant		ENST00000461988.6	NP_001382342.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POR	ENST00000461988.6 link	c.357+89C>T		intron_variant		1	NM_001395413.1	ENSP00000419970.2		P16435

Frequencies

GnomAD3 genomes

AF:

0.265

AC:

40310

AN:

151950

Hom.:

6172

Cov.:

show subpopulations

Gnomad AFR

AF:

0.134

Gnomad AMI

AF:

0.396

Gnomad AMR

AF:

0.256

Gnomad ASJ

AF:

0.245

Gnomad EAS

AF:

0.0330

Gnomad SAS

AF:

0.260

Gnomad FIN

AF:

0.321

Gnomad MID

AF:

0.253

Gnomad NFE

AF:

0.355

Gnomad OTH

AF:

0.284

GnomAD4 exome

AF:

0.325

AC:

451759

AN:

1388534

Hom.:

77407

Cov.:

AF XY:

0.324

AC XY:

222112

AN XY:

686380

show subpopulations

Gnomad4 AFR exome

AF:

0.125

Gnomad4 AMR exome

AF:

0.188

Gnomad4 ASJ exome

AF:

0.249

Gnomad4 EAS exome

AF:

0.0351

Gnomad4 SAS exome

AF:

0.259

Gnomad4 FIN exome

AF:

0.330

Gnomad4 NFE exome

AF:

0.355

Gnomad4 OTH exome

AF:

0.299

GnomAD4 genome

AF:

0.265

AC:

40300

AN:

152068

Hom.:

6166

Cov.:

AF XY:

0.261

AC XY:

19430

AN XY:

74346

show subpopulations

Gnomad4 AFR

AF:

0.134

Gnomad4 AMR

AF:

0.256

Gnomad4 ASJ

AF:

0.245

Gnomad4 EAS

AF:

0.0327

Gnomad4 SAS

AF:

0.260

Gnomad4 FIN

AF:

0.321

Gnomad4 NFE

AF:

0.355

Gnomad4 OTH

AF:

0.279

Alfa

AF:

0.331

Hom.:

7723

Bravo

AF:

0.250

Asia WGS

AF:

0.148

AC:

515

AN:

3478

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	Jun 26, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.56

DANN

Benign

0.79

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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