rs12899318

chr15-69021787-T-C

Variant summary

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

The NM_024505.4(NOX5):c.51-4741T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.392 in 152,128 control chromosomes in the GnomAD database, including 14,243 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 0.39 (14243 hom., cov: 32)
• Consequence: NOX5 NM_024505.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.268

Genes affected

NOX5 (HGNC:14874): (NADPH oxidase 5) This gene is predominantly expressed in the testis and lymphocyte-rich areas of spleen and lymph nodes. It encodes a calcium-dependen NADPH oxidase that generates superoxide, and functions as a calcium-dependent proton channel that may regulate redox-dependent processes in lymphocytes and spermatozoa. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Oct 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.546 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NOX5	NM_024505.4	c.51-4741T>C		intron_variant		ENST00000388866.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NOX5	ENST00000388866.8	c.51-4741T>C		intron_variant		1	NM_024505.4
NOX5	ENST00000530406.7	c.51-4741T>C		intron_variant		1		P1
NOX5	ENST00000527315.5	n.55-4741T>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.392 AC: 59632 AN: 152010 Hom.: 14249 Cov.: 32

Gnomad AFR AF: 0.156

Gnomad AMI AF: 0.509

Gnomad AMR AF: 0.367

Gnomad ASJ AF: 0.515

Gnomad EAS AF: 0.0648

Gnomad SAS AF: 0.320

Gnomad FIN AF: 0.477

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.550

Gnomad OTH AF: 0.414

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

GnomAD4 genome AF: 0.392 AC: 59609 AN: 152128 Hom.: 14243 Cov.: 32 AF XY: 0.384 AC XY: 28548 AN XY: 74364

Gnomad4 AFR AF: 0.155

Gnomad4 AMR AF: 0.366

Gnomad4 ASJ AF: 0.515

Gnomad4 EAS AF: 0.0638

Gnomad4 SAS AF: 0.319

Gnomad4 FIN AF: 0.477

Gnomad4 NFE AF: 0.550

Gnomad4 OTH AF: 0.409

Alfa AF: 0.459 Hom.: 2169

Bravo AF: 0.373

Asia WGS AF: 0.230 AC: 802 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	8.8
Dann	Benign	0.85

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: rs12899318; hg19: chr15-69314126;