rs781862803

Variant names:

• chr7-75954037-G-A
• rs781862803
• NM_001395413.1:c.36G>A

Your query was ambiguous. Multiple possible variants found:

• chr7-75954037-G-A
• chr7-75954037-G-T

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_001395413.1(POR):​c.36G>A​(p.Val12Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000755 in 1,457,260 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000075 (0 hom.)
• Consequence: POR NM_001395413.1 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.196
• Publications: 0 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 Submitted by: ClinGen, 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 -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 7-75954037-G-A is Benign according to our data. Variant chr7-75954037-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 1629869.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.196 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001395413.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POR	NM_001395413.1	MANE Select	c.36G>A	p.Val12Val	synonymous	Exon 2 of 16	NP_001382342.1	P16435
	POR	NM_001382655.3		c.36G>A	p.Val12Val	synonymous	Exon 2 of 17	NP_001369584.2
	POR	NM_001367562.3		c.36G>A	p.Val12Val	synonymous	Exon 3 of 17	NP_001354491.2	P16435

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POR	ENST00000461988.6	TSL:1 MANE Select	c.36G>A	p.Val12Val	synonymous	Exon 2 of 16	ENSP00000419970.2	P16435
	POR	ENST00000910548.1		c.36G>A	p.Val12Val	synonymous	Exon 2 of 16	ENSP00000580607.1
	POR	ENST00000910554.1		c.36G>A	p.Val12Val	synonymous	Exon 2 of 16	ENSP00000580613.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000415 AC: 1 AN: 240898 AF XY: 0.00000766

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000170

GnomAD4 exome AF: 0.00000755 AC: 11 AN: 1457260 Hom.: 0 Cov.: 31 AF XY: 0.00000690 AC XY: 5 AN XY: 724458

African (AFR) AF: 0.00 AC: 0 AN: 33418

American (AMR) AF: 0.000182 AC: 8 AN: 44000

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25986

East Asian (EAS) AF: 0.00 AC: 0 AN: 39582

South Asian (SAS) AF: 0.00 AC: 0 AN: 85340

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53136

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5724

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1109834

Other (OTH) AF: 0.0000166 AC: 1 AN: 60240

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Congenital adrenal hyperplasia due to cytochrome P450 oxidoreductase deficiency (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.2
DANN	Benign	0.53
PhyloP100		-0.20
PromoterAI		0.016	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=300/0	polymorphism

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: rs781862803; hg19: chr7-75583355;