7-75986787-G-A

Variant names:

• chr7-75986787-G-A
• rs17685
• NM_001395413.1:c.*306G>A

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.*306G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.28 in 574,552 control chromosomes in the GnomAD database, including 23,649 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.26 (5398 hom., cov: 34)
  • Exomes 𝑓: 0.29 (18251 hom.)
• Consequence: POR NM_001395413.1 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -4.47
• Publications: 75 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]

TMEM120A (HGNC:21697): (transmembrane protein 120A) Predicted to enable ion channel activity. Involved in fat cell differentiation; protein heterooligomerization; and protein homooligomerization. Predicted to be located in plasma membrane. Predicted to be active in membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BP6: Variant 7-75986787-G-A is Benign according to our data. Variant chr7-75986787-G-A is described in ClinVar as Benign. ClinVar VariationId is 360731.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.345 is higher than 0.05.

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.*306G>A		3_prime_UTR	Exon 16 of 16	NP_001382342.1	P16435
	POR	NM_001382655.3		c.*306G>A		3_prime_UTR	Exon 17 of 17	NP_001369584.2
	POR	NM_001367562.3		c.*306G>A		3_prime_UTR	Exon 17 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.*306G>A		3_prime_UTR	Exon 16 of 16	ENSP00000419970.2	P16435
	POR	ENST00000910548.1		c.*306G>A		3_prime_UTR	Exon 16 of 16	ENSP00000580607.1
	POR	ENST00000910554.1		c.*306G>A		3_prime_UTR	Exon 16 of 16	ENSP00000580613.1

Frequencies

GnomAD3 genomes AF: 0.258 AC: 39287 AN: 152006 Hom.: 5388 Cov.: 34

Gnomad AFR AF: 0.180

Gnomad AMI AF: 0.344

Gnomad AMR AF: 0.224

Gnomad ASJ AF: 0.233

Gnomad EAS AF: 0.358

Gnomad SAS AF: 0.347

Gnomad FIN AF: 0.399

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.278

Gnomad OTH AF: 0.259

GnomAD4 exome AF: 0.288 AC: 121518 AN: 422428 Hom.: 18251 Cov.: 0 AF XY: 0.291 AC XY: 64066 AN XY: 220346

African (AFR) AF: 0.179 AC: 2172 AN: 12142

American (AMR) AF: 0.217 AC: 3452 AN: 15924

Ashkenazi Jewish (ASJ) AF: 0.241 AC: 3220 AN: 13346

East Asian (EAS) AF: 0.361 AC: 10857 AN: 30114

South Asian (SAS) AF: 0.334 AC: 12544 AN: 37548

European-Finnish (FIN) AF: 0.387 AC: 11138 AN: 28774

Middle Eastern (MID) AF: 0.276 AC: 529 AN: 1914

European-Non Finnish (NFE) AF: 0.274 AC: 70704 AN: 257676

Other (OTH) AF: 0.276 AC: 6902 AN: 24990

GnomAD4 genome AF: 0.259 AC: 39327 AN: 152124 Hom.: 5398 Cov.: 34 AF XY: 0.266 AC XY: 19788 AN XY: 74374

African (AFR) AF: 0.181 AC: 7496 AN: 41512

American (AMR) AF: 0.224 AC: 3433 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.233 AC: 810 AN: 3472

East Asian (EAS) AF: 0.358 AC: 1847 AN: 5154

South Asian (SAS) AF: 0.346 AC: 1670 AN: 4822

European-Finnish (FIN) AF: 0.399 AC: 4228 AN: 10584

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.278 AC: 18914 AN: 67968

Other (OTH) AF: 0.260 AC: 549 AN: 2112

Alfa AF: 0.265 Hom.: 20662

Bravo AF: 0.239

Asia WGS AF: 0.318 AC: 1105 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	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	-0.66
CADD	Benign	0.039
DANN	Benign	0.86
PhyloP100		-4.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs17685; hg19: chr7-75616105;