rs28737229

Positions:

• chr7-75907418-T-G

Variant summary

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

The ENST00000453773.5(POR):​c.-14+8146T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.42 in 151,276 control chromosomes in the GnomAD database, including 13,865 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 0.42 (13865 hom., cov: 29)
• Consequence: POR ENST00000453773.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.168

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 = 0.458 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	ENST00000453773.5	c.-14+8146T>G		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.420 AC: 63476 AN: 151162 Hom.: 13852 Cov.: 29

Gnomad AFR AF: 0.425

Gnomad AMI AF: 0.512

Gnomad AMR AF: 0.363

Gnomad ASJ AF: 0.387

Gnomad EAS AF: 0.0273

Gnomad SAS AF: 0.427

Gnomad FIN AF: 0.395

Gnomad MID AF: 0.401

Gnomad NFE AF: 0.463

Gnomad OTH AF: 0.428

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

GnomAD4 genome AF: 0.420 AC: 63531 AN: 151276 Hom.: 13865 Cov.: 29 AF XY: 0.415 AC XY: 30660 AN XY: 73830

Gnomad4 AFR AF: 0.426

Gnomad4 AMR AF: 0.363

Gnomad4 ASJ AF: 0.387

Gnomad4 EAS AF: 0.0272

Gnomad4 SAS AF: 0.426

Gnomad4 FIN AF: 0.395

Gnomad4 NFE AF: 0.463

Gnomad4 OTH AF: 0.426

Alfa AF: 0.447 Hom.: 22330

Bravo AF: 0.413

Asia WGS AF: 0.227 AC: 792 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.8
DANN	Benign	0.55

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs28737229; hg19: chr7-75536736;