rs10239977

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

2

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]

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
PORNM_001395413.1 linkc.357+89C>T intron_variant ENST00000461988.6 NP_001382342.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PORENST00000461988.6 linkc.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.:
33
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.:
22
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.:
33
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 submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Benign, criteria provided, single submitterclinical testingGeneDxJun 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.

Other links and lift over

dbSNP: rs10239977; hg19: chr7-75608986; COSMIC: COSV67517099; COSMIC: COSV67517099; API