chr7-75984978-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001395413.1(POR):c.1239+20G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.298 in 1,572,946 control chromosomes in the GnomAD database, including 71,928 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.28 ( 5970 hom., cov: 32)

Exomes 𝑓: 0.30 ( 65958 hom. )

Consequence

POR
NM_001395413.1 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -0.143

Publications

16 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 Submitted by: ClinGen, 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

POR links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 7-75984978-G-A is Benign according to our data. Variant chr7-75984978-G-A is described in ClinVar as Benign. ClinVar VariationId is 256839.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.407 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001395413.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
POR	NM_001395413.1	MANE Select	c.1239+20G>A	intron	N/A	NP_001382342.1	P16435
POR	NM_001382655.3		c.1293+20G>A	intron	N/A	NP_001369584.2
POR	NM_001367562.3		c.1239+20G>A	intron	N/A	NP_001354491.2	P16435

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
POR	ENST00000461988.6	TSL:1 MANE Select	c.1239+20G>A	intron	N/A	ENSP00000419970.2	P16435
POR	ENST00000447222.5	TSL:5	c.1398+20G>A	intron	N/A	ENSP00000393527.1	H0Y4R2
POR	ENST00000910548.1		c.1239+20G>A	intron	N/A	ENSP00000580607.1

Frequencies

GnomAD3 genomes

AF:

0.275

AC:

41614

AN:

151246

Hom.:

5961

Cov.:

show subpopulations

Gnomad AFR

AF:

0.203

Gnomad AMI

AF:

0.230

Gnomad AMR

AF:

0.306

Gnomad ASJ

AF:

0.434

Gnomad EAS

AF:

0.421

Gnomad SAS

AF:

0.238

Gnomad FIN

AF:

0.238

Gnomad MID

AF:

0.446

Gnomad NFE

AF:

0.301

Gnomad OTH

AF:

0.288

GnomAD2 exomes

AF:

0.309

AC:

67880

AN:

219986

AF XY:

0.304

show subpopulations

Gnomad AFR exome

AF:

0.201

Gnomad AMR exome

AF:

0.364

Gnomad ASJ exome

AF:

0.423

Gnomad EAS exome

AF:

0.430

Gnomad FIN exome

AF:

0.233

Gnomad NFE exome

AF:

0.303

Gnomad OTH exome

AF:

0.315

GnomAD4 exome

AF:

0.301

AC:

427373

AN:

1421582

Hom.:

65958

Cov.:

AF XY:

0.300

AC XY:

210536

AN XY:

702378

show subpopulations

African (AFR)

AF:

0.200

AC:

6621

AN:

33040

American (AMR)

AF:

0.360

AC:

15553

AN:

43236

Ashkenazi Jewish (ASJ)

AF:

0.428

AC:

10348

AN:

24156

East Asian (EAS)

AF:

0.412

AC:

16114

AN:

39136

South Asian (SAS)

AF:

0.248

AC:

20404

AN:

82410

European-Finnish (FIN)

AF:

0.230

AC:

10294

AN:

44778

Middle Eastern (MID)

AF:

0.362

AC:

2019

AN:

5580

European-Non Finnish (NFE)

AF:

0.301

AC:

327705

AN:

1090456

Other (OTH)

AF:

0.312

AC:

18315

AN:

58790

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

16726

33452

50177

66903

83629

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11012

22024

33036

44048

55060

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.275

AC:

41649

AN:

151364

Hom.:

5970

Cov.:

AF XY:

0.272

AC XY:

20108

AN XY:

73942

show subpopulations

African (AFR)

AF:

0.203

AC:

8383

AN:

41302

American (AMR)

AF:

0.306

AC:

4649

AN:

15208

Ashkenazi Jewish (ASJ)

AF:

0.434

AC:

1493

AN:

3444

East Asian (EAS)

AF:

0.421

AC:

2153

AN:

5108

South Asian (SAS)

AF:

0.240

AC:

1153

AN:

4796

European-Finnish (FIN)

AF:

0.238

AC:

2505

AN:

10508

Middle Eastern (MID)

AF:

0.455

AC:

133

AN:

292

European-Non Finnish (NFE)

AF:

0.301

AC:

20358

AN:

67706

Other (OTH)

AF:

0.293

AC:

612

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1499

2997

4496

5994

7493

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

438

876

1314

1752

2190

<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:

0.277

Hom.:

607

Bravo

AF:

0.285

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (3)

not provided (2)

ADRENAL HYPERPLASIA, CONGENITAL, DUE TO 21-HYDROXYLASE DEFICIENCY (1)

Congenital adrenal hyperplasia due to cytochrome P450 oxidoreductase deficiency (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

1.1

(source)

DANN

Benign

0.44

PhyloP100

-0.14

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over