rs34990910

Positions:

• chr15-69039041-G-A
• chr15-69039041-G-C

Variant summary

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

The NM_024505.4(NOX5):​c.1504+52G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.042 in 1,595,492 control chromosomes in the GnomAD database, including 2,803 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 0.062 (481 hom., cov: 31)
  • Exomes 𝑓: 0.040 (2322 hom.)
• Consequence: NOX5 NM_024505.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.19

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]

NOX5 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.211 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NOX5	NM_024505.4	c.1504+52G>A		intron_variant		ENST00000388866.8	NP_078781.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NOX5	ENST00000388866.8	c.1504+52G>A		intron_variant		1	NM_024505.4	ENSP00000373518.3
NOX5	ENST00000260364.9	c.1450+52G>A		intron_variant		1		ENSP00000454143.1

Frequencies

GnomAD3 genomes AF: 0.0620 AC: 9421 AN: 152058 Hom.: 478 Cov.: 31

Gnomad AFR AF: 0.112

Gnomad AMI AF: 0.0132

Gnomad AMR AF: 0.0395

Gnomad ASJ AF: 0.0185

Gnomad EAS AF: 0.222

Gnomad SAS AF: 0.0797

Gnomad FIN AF: 0.0286

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0315

Gnomad OTH AF: 0.0549

GnomAD3 exomes AF: 0.0562 AC: 13994 AN: 249026 Hom.: 798 AF XY: 0.0547 AC XY: 7366 AN XY: 134676

Gnomad AFR exome AF: 0.116

Gnomad AMR exome AF: 0.0424

Gnomad ASJ exome AF: 0.0176

Gnomad EAS exome AF: 0.222

Gnomad SAS exome AF: 0.0766

Gnomad FIN exome AF: 0.0306

Gnomad NFE exome AF: 0.0284

Gnomad OTH exome AF: 0.0391

GnomAD4 exome AF: 0.0399 AC: 57582 AN: 1443316 Hom.: 2322 Cov.: 27 AF XY: 0.0402 AC XY: 28938 AN XY: 718978

Gnomad4 AFR exome AF: 0.123

Gnomad4 AMR exome AF: 0.0429

Gnomad4 ASJ exome AF: 0.0179

Gnomad4 EAS exome AF: 0.230

Gnomad4 SAS exome AF: 0.0744

Gnomad4 FIN exome AF: 0.0276

Gnomad4 NFE exome AF: 0.0286

Gnomad4 OTH exome AF: 0.0469

GnomAD4 genome AF: 0.0620 AC: 9433 AN: 152176 Hom.: 481 Cov.: 31 AF XY: 0.0622 AC XY: 4627 AN XY: 74388

Gnomad4 AFR AF: 0.112

Gnomad4 AMR AF: 0.0396

Gnomad4 ASJ AF: 0.0185

Gnomad4 EAS AF: 0.222

Gnomad4 SAS AF: 0.0797

Gnomad4 FIN AF: 0.0286

Gnomad4 NFE AF: 0.0315

Gnomad4 OTH AF: 0.0548

Alfa AF: 0.0255 Hom.: 19

Bravo AF: 0.0657

Asia WGS AF: 0.140 AC: 485 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.081
DANN	Benign	0.65

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: rs34990910; hg19: chr15-69331381; COSMIC: COSV52990805;