chr7-75984764-C-G

Position:

chr7-75984764-C-G

Variant summary

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

The NM_001395413.1(POR):c.1058-13C>G variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.935 in 1,611,828 control chromosomes in the GnomAD database, including 710,378 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.85 ( 57007 hom., cov: 33)

Exomes 𝑓: 0.94 ( 653371 hom. )

Consequence

POR
NM_001395413.1 splice_polypyrimidine_tract, intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -2.76

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=-0.97).

BP6

Variant 7-75984764-C-G is Benign according to our data. Variant chr7-75984764-C-G is described in ClinVar as [Benign]. Clinvar id is 138789.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-75984764-C-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.957 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.1058-13C>G		splice_polypyrimidine_tract_variant, intron_variant		ENST00000461988.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
POR	ENST00000461988.6 linkuse as main transcript	c.1058-13C>G		splice_polypyrimidine_tract_variant, intron_variant		1	NM_001395413.1	P4

Frequencies

GnomAD3 genomes

AF:

0.852

AC:

129552

AN:

152008

Hom.:

56976

Cov.:

show subpopulations

Gnomad AFR

AF:

0.610

Gnomad AMI

AF:

0.923

Gnomad AMR

AF:

0.871

Gnomad ASJ

AF:

0.973

Gnomad EAS

AF:

0.855

Gnomad SAS

AF:

0.919

Gnomad FIN

AF:

0.978

Gnomad MID

AF:

0.934

Gnomad NFE

AF:

0.963

Gnomad OTH

AF:

0.878

GnomAD3 exomes

AF:

0.911

AC:

225464

AN:

247390

Hom.:

103873

AF XY:

0.921

AC XY:

124107

AN XY:

134822

show subpopulations

Gnomad AFR exome

AF:

0.602

Gnomad AMR exome

AF:

0.840

Gnomad ASJ exome

AF:

0.975

Gnomad EAS exome

AF:

0.853

Gnomad SAS exome

AF:

0.922

Gnomad FIN exome

AF:

0.977

Gnomad NFE exome

AF:

0.963

Gnomad OTH exome

AF:

0.933

GnomAD4 exome

AF:

0.944

AC:

1377896

AN:

1459702

Hom.:

653371

Cov.:

AF XY:

0.945

AC XY:

686189

AN XY:

726174

show subpopulations

Gnomad4 AFR exome

AF:

0.596

Gnomad4 AMR exome

AF:

0.848

Gnomad4 ASJ exome

AF:

0.974

Gnomad4 EAS exome

AF:

0.862

Gnomad4 SAS exome

AF:

0.920

Gnomad4 FIN exome

AF:

0.975

Gnomad4 NFE exome

AF:

0.962

Gnomad4 OTH exome

AF:

0.924

GnomAD4 genome

AF:

0.852

AC:

129635

AN:

152126

Hom.:

57007

Cov.:

AF XY:

0.854

AC XY:

63476

AN XY:

74364

show subpopulations

Gnomad4 AFR

AF:

0.610

Gnomad4 AMR

AF:

0.871

Gnomad4 ASJ

AF:

0.973

Gnomad4 EAS

AF:

0.855

Gnomad4 SAS

AF:

0.919

Gnomad4 FIN

AF:

0.978

Gnomad4 NFE

AF:

0.963

Gnomad4 OTH

AF:

0.878

Alfa

AF:

0.916

Hom.:

11938

Bravo

AF:

0.832

Asia WGS

AF:

0.859

AC:

2988

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 21, 2014	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

Congenital adrenal hyperplasia due to cytochrome P450 oxidoreductase deficiency

Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -

Antley-Bixler syndrome with genital anomalies and disordered steroidogenesis

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Oct 25, 2021

- -

Classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency

Benign:1

Benign, criteria provided, single submitter

case-control

Pecori Giraldi Lab, University of Milan

This variant is intronic -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.97

CADD

Benign

0.22

DANN

Benign

0.38

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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