rs17685

Variant names:

Your query was ambiguous. Multiple possible variants found:

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.*306G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.28 in 574,552 control chromosomes in the GnomAD database, including 23,649 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.26 ( 5398 hom., cov: 34)

Exomes 𝑓: 0.29 ( 18251 hom. )

Consequence

POR
NM_001395413.1 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -4.47

Publications

75 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 links:

TMEM120A (HGNC:21697): (transmembrane protein 120A) Predicted to enable ion channel activity. Involved in fat cell differentiation; protein heterooligomerization; and protein homooligomerization. Predicted to be located in plasma membrane. Predicted to be active in membrane. [provided by Alliance of Genome Resources, Apr 2022]

TMEM120A 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=-0.66).

BP6

Variant 7-75986787-G-A is Benign according to our data. Variant chr7-75986787-G-A is described in ClinVar as Benign. ClinVar VariationId is 360731.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.345 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POR	NM_001395413.1 link	c.*306G>A		3_prime_UTR_variant	Exon 16 of 16	ENST00000461988.6	NP_001382342.1
TMEM120A	NM_031925.3 link	c.*385C>T		downstream_gene_variant		ENST00000493111.7	NP_114131.1	Q9BXJ8-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POR	ENST00000461988.6 link	c.*306G>A		3_prime_UTR_variant	Exon 16 of 16	1	NM_001395413.1	ENSP00000419970.2		P16435
TMEM120A	ENST00000493111.7 link	c.*385C>T		downstream_gene_variant		1	NM_031925.3	ENSP00000473983.1		Q9BXJ8-1

Frequencies

GnomAD3 genomes

AF:

0.258

AC:

39287

AN:

152006

Hom.:

5388

Cov.:

show subpopulations

Gnomad AFR

AF:

0.180

Gnomad AMI

AF:

0.344

Gnomad AMR

AF:

0.224

Gnomad ASJ

AF:

0.233

Gnomad EAS

AF:

0.358

Gnomad SAS

AF:

0.347

Gnomad FIN

AF:

0.399

Gnomad MID

AF:

0.212

Gnomad NFE

AF:

0.278

Gnomad OTH

AF:

0.259

GnomAD4 exome

AF:

0.288

AC:

121518

AN:

422428

Hom.:

18251

Cov.:

AF XY:

0.291

AC XY:

64066

AN XY:

220346

show subpopulations

African (AFR)

AF:

0.179

AC:

2172

AN:

12142

American (AMR)

AF:

0.217

AC:

3452

AN:

15924

Ashkenazi Jewish (ASJ)

AF:

0.241

AC:

3220

AN:

13346

East Asian (EAS)

AF:

0.361

AC:

10857

AN:

30114

South Asian (SAS)

AF:

0.334

AC:

12544

AN:

37548

European-Finnish (FIN)

AF:

0.387

AC:

11138

AN:

28774

Middle Eastern (MID)

AF:

0.276

AC:

529

AN:

1914

European-Non Finnish (NFE)

AF:

0.274

AC:

70704

AN:

257676

Other (OTH)

AF:

0.276

AC:

6902

AN:

24990

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

4257

8513

12770

17026

21283

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

422

844

1266

1688

2110

<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:

0.259

AC:

39327

AN:

152124

Hom.:

5398

Cov.:

AF XY:

0.266

AC XY:

19788

AN XY:

74374

show subpopulations

African (AFR)

AF:

0.181

AC:

7496

AN:

41512

American (AMR)

AF:

0.224

AC:

3433

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.233

AC:

810

AN:

3472

East Asian (EAS)

AF:

0.358

AC:

1847

AN:

5154

South Asian (SAS)

AF:

0.346

AC:

1670

AN:

4822

European-Finnish (FIN)

AF:

0.399

AC:

4228

AN:

10584

Middle Eastern (MID)

AF:

0.224

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.278

AC:

18914

AN:

67968

Other (OTH)

AF:

0.260

AC:

549

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1548

3096

4644

6192

7740

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

422

844

1266

1688

2110

<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:

0.265

Hom.:

20662

Bravo

AF:

0.239

Asia WGS

AF:

0.318

AC:

1105

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jun 26, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Congenital adrenal hyperplasia due to cytochrome P450 oxidoreductase deficiency

Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

0.039

(source)

DANN

Benign

0.86

PhyloP100

-4.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over