rs10954724

chr7-75968227-C-T

Variant summary

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

The NM_001395413.1(POR):c.180-4186C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.557 in 466,008 control chromosomes in the GnomAD database, including 73,656 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 0.54 (22244 hom., cov: 33)
  • Exomes 𝑓: 0.57 (51412 hom.)
• Consequence: POR NM_001395413.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.470

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 = 0.596 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
POR	NM_001395413.1	c.180-4186C>T		intron_variant		ENST00000461988.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
POR	ENST00000461988.6	c.180-4186C>T		intron_variant		1	NM_001395413.1	P4

Frequencies

GnomAD3 genomes AF: 0.536 AC: 81384 AN: 151966 Hom.: 22230 Cov.: 33

Gnomad AFR AF: 0.439

Gnomad AMI AF: 0.479

Gnomad AMR AF: 0.530

Gnomad ASJ AF: 0.631

Gnomad EAS AF: 0.465

Gnomad SAS AF: 0.530

Gnomad FIN AF: 0.506

Gnomad MID AF: 0.677

Gnomad NFE AF: 0.601

Gnomad OTH AF: 0.550

GnomAD3 exomes AF: 0.552 AC: 79451 AN: 143996 Hom.: 22240 AF XY: 0.556 AC XY: 43277 AN XY: 77886

Gnomad AFR exome AF: 0.434

Gnomad AMR exome AF: 0.520

Gnomad ASJ exome AF: 0.619

Gnomad EAS exome AF: 0.473

Gnomad SAS exome AF: 0.537

Gnomad FIN exome AF: 0.509

Gnomad NFE exome AF: 0.602

Gnomad OTH exome AF: 0.570

GnomAD4 exome AF: 0.568 AC: 178339 AN: 313922 Hom.: 51412 Cov.: 0 AF XY: 0.567 AC XY: 100877 AN XY: 177798

Gnomad4 AFR exome AF: 0.443

Gnomad4 AMR exome AF: 0.520

Gnomad4 ASJ exome AF: 0.613

Gnomad4 EAS exome AF: 0.465

Gnomad4 SAS exome AF: 0.535

Gnomad4 FIN exome AF: 0.508

Gnomad4 NFE exome AF: 0.606

Gnomad4 OTH exome AF: 0.584

GnomAD4 genome AF: 0.535 AC: 81441 AN: 152086 Hom.: 22244 Cov.: 33 AF XY: 0.528 AC XY: 39244 AN XY: 74352

Gnomad4 AFR AF: 0.439

Gnomad4 AMR AF: 0.529

Gnomad4 ASJ AF: 0.631

Gnomad4 EAS AF: 0.465

Gnomad4 SAS AF: 0.532

Gnomad4 FIN AF: 0.506

Gnomad4 NFE AF: 0.601

Gnomad4 OTH AF: 0.552

Alfa AF: 0.566 Hom.: 10817

Bravo AF: 0.536

Asia WGS AF: 0.480 AC: 1668 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	2.4
Dann	Benign	0.82

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

Other links and lift over

dbSNP: rs10954724; hg19: chr7-75597545; COSMIC: COSV67516125;