rs72553971

chr7-75914929-C-A

Variant summary

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

The ENST00000439963.5(POR):c.-14+7298C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0402 in 152,492 control chromosomes in the GnomAD database, including 172 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 0.040 (170 hom., cov: 32)
  • Exomes 𝑓: 0.089 (2 hom.)
• Consequence: POR ENST00000439963.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.83

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=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0606 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+7298C>A		intron_variant		4
POR	ENST00000453773.5	c.-14+15657C>A		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.0402 AC: 6123 AN: 152212 Hom.: 170 Cov.: 32

Gnomad AFR AF: 0.0107

Gnomad AMI AF: 0.0340

Gnomad AMR AF: 0.0320

Gnomad ASJ AF: 0.0573

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0252

Gnomad FIN AF: 0.0455

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0621

Gnomad OTH AF: 0.0482

GnomAD4 exome AF: 0.0893 AC: 15 AN: 168 Hom.: 2 AF XY: 0.0917 AC XY: 11 AN XY: 120

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.167

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0985

Gnomad4 OTH exome AF: 0.125

GnomAD4 genome AF: 0.0402 AC: 6121 AN: 152324 Hom.: 170 Cov.: 32 AF XY: 0.0388 AC XY: 2890 AN XY: 74482

Gnomad4 AFR AF: 0.0107

Gnomad4 AMR AF: 0.0320

Gnomad4 ASJ AF: 0.0573

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0252

Gnomad4 FIN AF: 0.0455

Gnomad4 NFE AF: 0.0621

Gnomad4 OTH AF: 0.0473

Alfa AF: 0.0527 Hom.: 46

Bravo AF: 0.0376

Asia WGS AF: 0.0110 AC: 40 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	0.44
Dann	Benign	0.43

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs72553971; hg19: chr7-75544247;