rs2868180

Positions:

• chr7-75961490-T-C

Variant summary

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

The NM_001395413.1(POR):​c.179+7310T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.411 in 151,946 control chromosomes in the GnomAD database, including 13,795 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 0.41 (13795 hom., cov: 31)
• Consequence: POR NM_001395413.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.392

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.567 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
POR	NM_001395413.1	c.179+7310T>C		intron_variant		ENST00000461988.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
POR	ENST00000461988.6	c.179+7310T>C		intron_variant		1	NM_001395413.1	P4

Frequencies

GnomAD3 genomes AF: 0.411 AC: 62347 AN: 151828 Hom.: 13767 Cov.: 31

Gnomad AFR AF: 0.573

Gnomad AMI AF: 0.255

Gnomad AMR AF: 0.421

Gnomad ASJ AF: 0.448

Gnomad EAS AF: 0.452

Gnomad SAS AF: 0.295

Gnomad FIN AF: 0.289

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.334

Gnomad OTH AF: 0.398

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

GnomAD4 genome AF: 0.411 AC: 62429 AN: 151946 Hom.: 13795 Cov.: 31 AF XY: 0.405 AC XY: 30067 AN XY: 74290

Gnomad4 AFR AF: 0.573

Gnomad4 AMR AF: 0.421

Gnomad4 ASJ AF: 0.448

Gnomad4 EAS AF: 0.452

Gnomad4 SAS AF: 0.296

Gnomad4 FIN AF: 0.289

Gnomad4 NFE AF: 0.334

Gnomad4 OTH AF: 0.402

Alfa AF: 0.353 Hom.: 20202

Bravo AF: 0.438

Asia WGS AF: 0.393 AC: 1366 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.7
DANN	Benign	0.61

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: rs2868180; hg19: chr7-75590808;