rs7804806

Positions:

• chr7-75966364-A-G
• chr7-75966364-A-T

Variant summary

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

The ENST00000461988.6(POR):​c.180-6049A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.684 in 152,064 control chromosomes in the GnomAD database, including 35,754 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 0.68 (35754 hom., cov: 31)
• Consequence: POR ENST00000461988.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.320

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 (SAS) allele frequency at 95% confidence interval = 0.727 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POR	NM_001395413.1	c.180-6049A>G		intron_variant		ENST00000461988.6	NP_001382342.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POR	ENST00000461988.6	c.180-6049A>G		intron_variant		1	NM_001395413.1	ENSP00000419970	P4

Frequencies

GnomAD3 genomes AF: 0.684 AC: 103898 AN: 151946 Hom.: 35735 Cov.: 31

Gnomad AFR AF: 0.678

Gnomad AMI AF: 0.794

Gnomad AMR AF: 0.675

Gnomad ASJ AF: 0.574

Gnomad EAS AF: 0.576

Gnomad SAS AF: 0.749

Gnomad FIN AF: 0.768

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.685

Gnomad OTH AF: 0.682

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

GnomAD4 genome AF: 0.684 AC: 103957 AN: 152064 Hom.: 35754 Cov.: 31 AF XY: 0.690 AC XY: 51259 AN XY: 74338

Gnomad4 AFR AF: 0.677

Gnomad4 AMR AF: 0.675

Gnomad4 ASJ AF: 0.574

Gnomad4 EAS AF: 0.575

Gnomad4 SAS AF: 0.747

Gnomad4 FIN AF: 0.768

Gnomad4 NFE AF: 0.685

Gnomad4 OTH AF: 0.677

Alfa AF: 0.676 Hom.: 26002

Bravo AF: 0.667

Asia WGS AF: 0.671 AC: 2333 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	3.7
DANN	Benign	0.41

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs7804806; hg19: chr7-75595682;