7-75899819-C-T

Position:

• chr7-75899819-C-T

Variant summary

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

The ENST00000453773.5(POR):​c.-14+547C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.198 in 152,088 control chromosomes in the GnomAD database, including 3,135 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 0.20 (3135 hom., cov: 32)
• Consequence: POR ENST00000453773.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.272

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=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.221 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POR	ENST00000453773.5	c.-14+547C>T		intron_variant		4		ENSP00000395813

Frequencies

GnomAD3 genomes AF: 0.198 AC: 30095 AN: 151970 Hom.: 3134 Cov.: 32

Gnomad AFR AF: 0.189

Gnomad AMI AF: 0.251

Gnomad AMR AF: 0.174

Gnomad ASJ AF: 0.186

Gnomad EAS AF: 0.0166

Gnomad SAS AF: 0.191

Gnomad FIN AF: 0.184

Gnomad MID AF: 0.277

Gnomad NFE AF: 0.224

Gnomad OTH AF: 0.212

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

GnomAD4 genome AF: 0.198 AC: 30123 AN: 152088 Hom.: 3135 Cov.: 32 AF XY: 0.195 AC XY: 14475 AN XY: 74342

Gnomad4 AFR AF: 0.189

Gnomad4 AMR AF: 0.174

Gnomad4 ASJ AF: 0.186

Gnomad4 EAS AF: 0.0166

Gnomad4 SAS AF: 0.193

Gnomad4 FIN AF: 0.184

Gnomad4 NFE AF: 0.224

Gnomad4 OTH AF: 0.210

Alfa AF: 0.221 Hom.: 3890

Bravo AF: 0.195

Asia WGS AF: 0.106 AC: 370 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.72
DANN	Benign	0.45

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10280802; hg19: chr7-75529137;