rs11579965

Positions:

• chr1-183594026-C-G

Variant summary

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

The XM_047421222.1(NCF2):​c.-143-1460G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.098 in 152,234 control chromosomes in the GnomAD database, including 836 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 0.098 (836 hom., cov: 33)
• Consequence: NCF2 XM_047421222.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.739

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=-0.86).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.149 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NCF2	XM_047421222.1	c.-143-1460G>C		intron_variant			XP_047277178.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SMG7	ENST00000495321.1	n.234-3743C>G		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.0979 AC: 14893 AN: 152118 Hom.: 832 Cov.: 33

Gnomad AFR AF: 0.132

Gnomad AMI AF: 0.144

Gnomad AMR AF: 0.154

Gnomad ASJ AF: 0.0746

Gnomad EAS AF: 0.0342

Gnomad SAS AF: 0.0763

Gnomad FIN AF: 0.0992

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0719

Gnomad OTH AF: 0.0874

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

GnomAD4 genome AF: 0.0980 AC: 14919 AN: 152234 Hom.: 836 Cov.: 33 AF XY: 0.0998 AC XY: 7427 AN XY: 74432

Gnomad4 AFR AF: 0.132

Gnomad4 AMR AF: 0.154

Gnomad4 ASJ AF: 0.0746

Gnomad4 EAS AF: 0.0341

Gnomad4 SAS AF: 0.0768

Gnomad4 FIN AF: 0.0992

Gnomad4 NFE AF: 0.0719

Gnomad4 OTH AF: 0.0865

Alfa AF: 0.0883 Hom.: 90

Bravo AF: 0.104

Asia WGS AF: 0.0610 AC: 212 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	7.3
DANN	Benign	0.43

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs11579965; hg19: chr1-183563161;