chr15-69021787-T-C

Variant names:

• chr15-69021787-T-C
• rs12899318
• NM_024505.4:c.51-4741T>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.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
• Publications: 2 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=-0.91).
• 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 rank	MANE	Protein	UniProt
NOX5	NM_024505.4	c.51-4741T>C		intron_variant	Intron 1 of 15	ENST00000388866.8	NP_078781.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOX5	ENST00000388866.8	c.51-4741T>C		intron_variant	Intron 1 of 15	1	NM_024505.4	ENSP00000373518.3
SPESP1-NOX5	ENST00000703585.1	c.30-4741T>C		intron_variant	Intron 1 of 15			ENSP00000515387.1

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

African (AFR) AF: 0.155 AC: 6449 AN: 41514

American (AMR) AF: 0.366 AC: 5596 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.515 AC: 1786 AN: 3466

East Asian (EAS) AF: 0.0638 AC: 331 AN: 5186

South Asian (SAS) AF: 0.319 AC: 1539 AN: 4822

European-Finnish (FIN) AF: 0.477 AC: 5038 AN: 10562

Middle Eastern (MID) AF: 0.408 AC: 120 AN: 294

European-Non Finnish (NFE) AF: 0.550 AC: 37420 AN: 67980

Other (OTH) AF: 0.409 AC: 866 AN: 2116

Alfa AF: 0.446 Hom.: 2174

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
PhyloP100		0.27
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: rs12899318; hg19: chr15-69314126;