rs231950

Positions:

• chr6-155428027-G-A
• chr6-155428027-G-C

Variant summary

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

The NM_015718.3(NOX3):​c.1145+767C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.482 in 151,980 control chromosomes in the GnomAD database, including 18,101 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 0.48 (18101 hom., cov: 33)
• Consequence: NOX3 NM_015718.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.63

Genes affected

NOX3 (HGNC:7890): (NADPH oxidase 3) This gene encodes a member of the NOX family of NADPH oxidases. These enzymes have the capacity to generate superoxide and other reactive oxygen species (ROS) and transport electrons across the plasma membrane. The ROS generated by family members have been implicated in numerous biological functions including host defense, posttranlational processing of proteins, cellular signaling, regulation of gene expression, and cell differentiation. The protein encoded by this gene is expressed predominantly in the inner ear and is involved in the biogenesis of otoconia/otolith, which are crystalline structures of the inner ear involved in the perception of gravity.[provided by RefSeq, May 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.51 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NOX3	NM_015718.3	c.1145+767C>T		intron_variant		ENST00000159060.3	NP_056533.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NOX3	ENST00000159060.3	c.1145+767C>T		intron_variant		1	NM_015718.3	ENSP00000159060	P1

Frequencies

GnomAD3 genomes AF: 0.482 AC: 73179 AN: 151862 Hom.: 18091 Cov.: 33

Gnomad AFR AF: 0.470

Gnomad AMI AF: 0.497

Gnomad AMR AF: 0.520

Gnomad ASJ AF: 0.570

Gnomad EAS AF: 0.153

Gnomad SAS AF: 0.463

Gnomad FIN AF: 0.508

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.499

Gnomad OTH AF: 0.475

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

GnomAD4 genome AF: 0.482 AC: 73225 AN: 151980 Hom.: 18101 Cov.: 33 AF XY: 0.479 AC XY: 35579 AN XY: 74288

Gnomad4 AFR AF: 0.469

Gnomad4 AMR AF: 0.520

Gnomad4 ASJ AF: 0.570

Gnomad4 EAS AF: 0.153

Gnomad4 SAS AF: 0.465

Gnomad4 FIN AF: 0.508

Gnomad4 NFE AF: 0.499

Gnomad4 OTH AF: 0.473

Alfa AF: 0.490 Hom.: 2202

Bravo AF: 0.478

Asia WGS AF: 0.351 AC: 1221 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.38
DANN	Benign	0.74

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: rs231950; hg19: chr6-155749161; COSMIC: COSV50161729;