rs17148944

Positions:

• chr7-75972549-G-A
• chr7-75972549-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001395413.1(POR):​c.228+88G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0924 in 1,270,272 control chromosomes in the GnomAD database, including 6,199 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.076 (572 hom., cov: 32)
  • Exomes 𝑓: 0.095 (5627 hom.)
• Consequence: POR NM_001395413.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0350

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 7-75972549-G-A is Benign according to our data. Variant chr7-75972549-G-A is described in ClinVar as [Benign]. Clinvar id is 1264470.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.142 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
POR	NM_001395413.1	c.228+88G>A		intron_variant		ENST00000461988.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
POR	ENST00000461988.6	c.228+88G>A		intron_variant		1	NM_001395413.1	P4

Frequencies

GnomAD3 genomes AF: 0.0759 AC: 11556 AN: 152198 Hom.: 571 Cov.: 32

Gnomad AFR AF: 0.0439

Gnomad AMI AF: 0.308

Gnomad AMR AF: 0.0627

Gnomad ASJ AF: 0.0937

Gnomad EAS AF: 0.00424

Gnomad SAS AF: 0.152

Gnomad FIN AF: 0.0439

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.0989

Gnomad OTH AF: 0.0894

GnomAD3 exomes AF: 0.0849 AC: 13324 AN: 156952 Hom.: 695 AF XY: 0.0918 AC XY: 7625 AN XY: 83078

Gnomad AFR exome AF: 0.0402

Gnomad AMR exome AF: 0.0484

Gnomad ASJ exome AF: 0.0947

Gnomad EAS exome AF: 0.00318

Gnomad SAS exome AF: 0.156

Gnomad FIN exome AF: 0.0490

Gnomad NFE exome AF: 0.101

Gnomad OTH exome AF: 0.0925

GnomAD4 exome AF: 0.0946 AC: 105789 AN: 1117956 Hom.: 5627 Cov.: 15 AF XY: 0.0975 AC XY: 54986 AN XY: 563828

Gnomad4 AFR exome AF: 0.0421

Gnomad4 AMR exome AF: 0.0520

Gnomad4 ASJ exome AF: 0.0966

Gnomad4 EAS exome AF: 0.00159

Gnomad4 SAS exome AF: 0.153

Gnomad4 FIN exome AF: 0.0501

Gnomad4 NFE exome AF: 0.0995

Gnomad4 OTH exome AF: 0.0874

GnomAD4 genome AF: 0.0759 AC: 11565 AN: 152316 Hom.: 572 Cov.: 32 AF XY: 0.0751 AC XY: 5597 AN XY: 74496

Gnomad4 AFR AF: 0.0439

Gnomad4 AMR AF: 0.0626

Gnomad4 ASJ AF: 0.0937

Gnomad4 EAS AF: 0.00405

Gnomad4 SAS AF: 0.151

Gnomad4 FIN AF: 0.0439

Gnomad4 NFE AF: 0.0990

Gnomad4 OTH AF: 0.0918

Alfa AF: 0.0957 Hom.: 693

Bravo AF: 0.0733

Asia WGS AF: 0.0750 AC: 265 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 17, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.0
DANN	Benign	0.73

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: rs17148944; hg19: chr7-75601867; COSMIC: COSV67516496;