1-183580622-G-T

Position:

• chr1-183580622-G-T

Variant summary

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

The NM_000433.4(NCF2):​c.258-2915C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.304 in 151,918 control chromosomes in the GnomAD database, including 7,217 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 0.30 (7217 hom., cov: 31)
• Consequence: NCF2 NM_000433.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.140

Genes affected

NCF2 (HGNC:7661): (neutrophil cytosolic factor 2) This gene encodes neutrophil cytosolic factor 2, the 67-kilodalton cytosolic subunit of the multi-protein NADPH oxidase complex found in neutrophils. This oxidase produces a burst of superoxide which is delivered to the lumen of the neutrophil phagosome. Mutations in this gene, as well as in other NADPH oxidase subunits, can result in chronic granulomatous disease, a disease that causes recurrent infections by catalase-positive organisms. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jun 2010]

SMG7 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.53 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NCF2	NM_000433.4	c.258-2915C>A		intron_variant		ENST00000367535.8	NP_000424.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NCF2	ENST00000367535.8	c.258-2915C>A		intron_variant		1	NM_000433.4	ENSP00000356505.4

Frequencies

GnomAD3 genomes AF: 0.304 AC: 46128 AN: 151798 Hom.: 7209 Cov.: 31

Gnomad AFR AF: 0.311

Gnomad AMI AF: 0.363

Gnomad AMR AF: 0.336

Gnomad ASJ AF: 0.268

Gnomad EAS AF: 0.547

Gnomad SAS AF: 0.377

Gnomad FIN AF: 0.254

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.278

Gnomad OTH AF: 0.304

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

GnomAD4 genome AF: 0.304 AC: 46158 AN: 151918 Hom.: 7217 Cov.: 31 AF XY: 0.305 AC XY: 22679 AN XY: 74236

Gnomad4 AFR AF: 0.310

Gnomad4 AMR AF: 0.336

Gnomad4 ASJ AF: 0.268

Gnomad4 EAS AF: 0.547

Gnomad4 SAS AF: 0.374

Gnomad4 FIN AF: 0.254

Gnomad4 NFE AF: 0.278

Gnomad4 OTH AF: 0.307

Alfa AF: 0.282 Hom.: 1647

Bravo AF: 0.311

Asia WGS AF: 0.485 AC: 1680 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.9
DANN	Benign	0.51

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: rs10911363; hg19: chr1-183549757;