rs2286823

Variant names:

• chr7-75984978-G-A
• rs2286823
• NM_001395413.1:c.1239+20G>A

Your query was ambiguous. Multiple possible variants found:

• chr7-75984978-G-A
• chr7-75984978-G-C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001395413.1(POR):​c.1239+20G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.298 in 1,572,946 control chromosomes in the GnomAD database, including 71,928 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.28 (5970 hom., cov: 32)
  • Exomes 𝑓: 0.30 (65958 hom.)
• Consequence: POR NM_001395413.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -0.143
• Publications: 16 publications found

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]

POR Gene-Disease associations (from GenCC):

• Antley-Bixler syndrome with genital anomalies and disordered steroidogenesis

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: ClinGen, PanelApp Australia, Ambry Genetics
• congenital adrenal hyperplasia due to cytochrome P450 oxidoreductase deficiency

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet
• Antley-Bixler syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 7-75984978-G-A is Benign according to our data. Variant chr7-75984978-G-A is described in ClinVar as Benign. ClinVar VariationId is 256839.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.407 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POR	NM_001395413.1	c.1239+20G>A		intron_variant	Intron 11 of 15	ENST00000461988.6	NP_001382342.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POR	ENST00000461988.6	c.1239+20G>A		intron_variant	Intron 11 of 15	1	NM_001395413.1	ENSP00000419970.2

Frequencies

GnomAD3 genomes AF: 0.275 AC: 41614 AN: 151246 Hom.: 5961 Cov.: 32

Gnomad AFR AF: 0.203

Gnomad AMI AF: 0.230

Gnomad AMR AF: 0.306

Gnomad ASJ AF: 0.434

Gnomad EAS AF: 0.421

Gnomad SAS AF: 0.238

Gnomad FIN AF: 0.238

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.301

Gnomad OTH AF: 0.288

GnomAD2 exomes AF: 0.309 AC: 67880 AN: 219986 AF XY: 0.304

Gnomad AFR exome AF: 0.201

Gnomad AMR exome AF: 0.364

Gnomad ASJ exome AF: 0.423

Gnomad EAS exome AF: 0.430

Gnomad FIN exome AF: 0.233

Gnomad NFE exome AF: 0.303

Gnomad OTH exome AF: 0.315

GnomAD4 exome AF: 0.301 AC: 427373 AN: 1421582 Hom.: 65958 Cov.: 43 AF XY: 0.300 AC XY: 210536 AN XY: 702378

African (AFR) AF: 0.200 AC: 6621 AN: 33040

American (AMR) AF: 0.360 AC: 15553 AN: 43236

Ashkenazi Jewish (ASJ) AF: 0.428 AC: 10348 AN: 24156

East Asian (EAS) AF: 0.412 AC: 16114 AN: 39136

South Asian (SAS) AF: 0.248 AC: 20404 AN: 82410

European-Finnish (FIN) AF: 0.230 AC: 10294 AN: 44778

Middle Eastern (MID) AF: 0.362 AC: 2019 AN: 5580

European-Non Finnish (NFE) AF: 0.301 AC: 327705 AN: 1090456

Other (OTH) AF: 0.312 AC: 18315 AN: 58790

GnomAD4 genome AF: 0.275 AC: 41649 AN: 151364 Hom.: 5970 Cov.: 32 AF XY: 0.272 AC XY: 20108 AN XY: 73942

African (AFR) AF: 0.203 AC: 8383 AN: 41302

American (AMR) AF: 0.306 AC: 4649 AN: 15208

Ashkenazi Jewish (ASJ) AF: 0.434 AC: 1493 AN: 3444

East Asian (EAS) AF: 0.421 AC: 2153 AN: 5108

South Asian (SAS) AF: 0.240 AC: 1153 AN: 4796

European-Finnish (FIN) AF: 0.238 AC: 2505 AN: 10508

Middle Eastern (MID) AF: 0.455 AC: 133 AN: 292

European-Non Finnish (NFE) AF: 0.301 AC: 20358 AN: 67706

Other (OTH) AF: 0.293 AC: 612 AN: 2088

Alfa AF: 0.277 Hom.: 607

Bravo AF: 0.285

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

-

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided Benign:2

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Congenital adrenal hyperplasia due to cytochrome P450 oxidoreductase deficiency Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency Benign:1

-

Pecori Giraldi Lab, University of Milan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: case-control

This variant is intronic -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.1
DANN	Benign	0.44
PhyloP100		-0.14
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2286823; hg19: chr7-75614296; COSMIC: COSV58694823; COSMIC: COSV58694823;