7-75914894-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000439963.5(POR):c.-14+7263C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0712 in 152,256 control chromosomes in the GnomAD database, including 477 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.071 (477 hom., cov: 32)
• Consequence: POR ENST00000439963.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.82

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0933 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
POR	ENST00000439963.5	c.-14+7263C>T		intron_variant		4
POR	ENST00000453773.5	c.-14+15622C>T		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.0712 AC: 10833 AN: 152140 Hom.: 478 Cov.: 32

Gnomad AFR AF: 0.0411

Gnomad AMI AF: 0.0736

Gnomad AMR AF: 0.0602

Gnomad ASJ AF: 0.132

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0230

Gnomad FIN AF: 0.0828

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.0952

Gnomad OTH AF: 0.0828

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0712 AC: 10834 AN: 152256 Hom.: 477 Cov.: 32 AF XY: 0.0695 AC XY: 5172 AN XY: 74448

Gnomad4 AFR AF: 0.0411

Gnomad4 AMR AF: 0.0602

Gnomad4 ASJ AF: 0.132

Gnomad4 EAS AF: 0.000194

Gnomad4 SAS AF: 0.0232

Gnomad4 FIN AF: 0.0828

Gnomad4 NFE AF: 0.0952

Gnomad4 OTH AF: 0.0819

Alfa AF: 0.0413 Hom.: 49

Bravo AF: 0.0691

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	0.24
Dann	Benign	0.78

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12537282; hg19: chr7-75544212;