7-75982438-C-T

Variant names:

• chr7-75982438-C-T
• rs3815455
• NM_001395413.1:c.821+116C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001395413.1(POR):​c.821+116C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.291 in 847,838 control chromosomes in the GnomAD database, including 38,174 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.28 (6141 hom., cov: 32)
  • Exomes 𝑓: 0.29 (32033 hom.)
• Consequence: POR NM_001395413.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.880
• Publications: 15 publications found

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, STRONG Submitted by: ClinGen, PanelApp Australia, 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

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 7-75982438-C-T is Benign according to our data. Variant chr7-75982438-C-T is described in ClinVar as Benign. ClinVar VariationId is 1252414.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.368 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POR	NM_001395413.1	c.821+116C>T		intron_variant	Intron 8 of 15	ENST00000461988.6	NP_001382342.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POR	ENST00000461988.6	c.821+116C>T		intron_variant	Intron 8 of 15	1	NM_001395413.1	ENSP00000419970.2

Frequencies

GnomAD3 genomes AF: 0.275 AC: 41770 AN: 151892 Hom.: 6131 Cov.: 32

Gnomad AFR AF: 0.184

Gnomad AMI AF: 0.343

Gnomad AMR AF: 0.293

Gnomad ASJ AF: 0.285

Gnomad EAS AF: 0.381

Gnomad SAS AF: 0.360

Gnomad FIN AF: 0.414

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.289

Gnomad OTH AF: 0.279

GnomAD4 exome AF: 0.295 AC: 205219 AN: 695828 Hom.: 32033 AF XY: 0.299 AC XY: 106906 AN XY: 357838

African (AFR) AF: 0.176 AC: 3235 AN: 18410

American (AMR) AF: 0.286 AC: 9065 AN: 31656

Ashkenazi Jewish (ASJ) AF: 0.285 AC: 4985 AN: 17488

East Asian (EAS) AF: 0.401 AC: 12833 AN: 31968

South Asian (SAS) AF: 0.352 AC: 20000 AN: 56776

European-Finnish (FIN) AF: 0.406 AC: 14902 AN: 36666

Middle Eastern (MID) AF: 0.279 AC: 959 AN: 3442

European-Non Finnish (NFE) AF: 0.278 AC: 129436 AN: 465106

Other (OTH) AF: 0.286 AC: 9804 AN: 34316

GnomAD4 genome AF: 0.275 AC: 41809 AN: 152010 Hom.: 6141 Cov.: 32 AF XY: 0.284 AC XY: 21120 AN XY: 74286

African (AFR) AF: 0.184 AC: 7652 AN: 41500

American (AMR) AF: 0.293 AC: 4474 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.285 AC: 990 AN: 3470

East Asian (EAS) AF: 0.382 AC: 1961 AN: 5138

South Asian (SAS) AF: 0.359 AC: 1732 AN: 4828

European-Finnish (FIN) AF: 0.414 AC: 4378 AN: 10568

Middle Eastern (MID) AF: 0.228 AC: 67 AN: 294

European-Non Finnish (NFE) AF: 0.289 AC: 19651 AN: 67914

Other (OTH) AF: 0.280 AC: 592 AN: 2112

Alfa AF: 0.264 Hom.: 1233

Bravo AF: 0.259

Asia WGS AF: 0.336 AC: 1169 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.8
DANN	Benign	0.52
PhyloP100		-0.88
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3815455; hg19: chr7-75611756; COSMIC: COSV58695035; COSMIC: COSV58695035;