chr15-69054606-T-C

Variant names:

• chr15-69054606-T-C
• rs311904
• NM_024505.4:c.2000-728T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024505.4(NOX5):​c.2000-728T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.836 in 152,200 control chromosomes in the GnomAD database, including 55,383 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 0.84 (55383 hom., cov: 32)
• Consequence: NOX5 NM_024505.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.180
• Publications: 6 publications found

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]

SPESP1-NOX5 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.959 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOX5	NM_024505.4	c.2000-728T>C		intron_variant	Intron 14 of 15	ENST00000388866.8	NP_078781.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOX5	ENST00000388866.8	c.2000-728T>C		intron_variant	Intron 14 of 15	1	NM_024505.4	ENSP00000373518.3
SPESP1-NOX5	ENST00000703585.1	c.1895-728T>C		intron_variant	Intron 14 of 15			ENSP00000515387.1

Frequencies

GnomAD3 genomes AF: 0.836 AC: 127151 AN: 152082 Hom.: 55360 Cov.: 32

Gnomad AFR AF: 0.589

Gnomad AMI AF: 0.987

Gnomad AMR AF: 0.884

Gnomad ASJ AF: 0.975

Gnomad EAS AF: 0.594

Gnomad SAS AF: 0.906

Gnomad FIN AF: 0.925

Gnomad MID AF: 0.943

Gnomad NFE AF: 0.965

Gnomad OTH AF: 0.858

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

GnomAD4 genome AF: 0.836 AC: 127221 AN: 152200 Hom.: 55383 Cov.: 32 AF XY: 0.836 AC XY: 62206 AN XY: 74420

African (AFR) AF: 0.589 AC: 24450 AN: 41482

American (AMR) AF: 0.884 AC: 13521 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.975 AC: 3385 AN: 3472

East Asian (EAS) AF: 0.593 AC: 3061 AN: 5162

South Asian (SAS) AF: 0.905 AC: 4373 AN: 4830

European-Finnish (FIN) AF: 0.925 AC: 9823 AN: 10618

Middle Eastern (MID) AF: 0.939 AC: 276 AN: 294

European-Non Finnish (NFE) AF: 0.965 AC: 65620 AN: 68018

Other (OTH) AF: 0.858 AC: 1812 AN: 2112

Alfa AF: 0.896 Hom.: 28440

Bravo AF: 0.818

Asia WGS AF: 0.764 AC: 2658 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	6.0
DANN	Benign	0.50
PhyloP100		0.18
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: rs311904; hg19: chr15-69346946;