1-183596965-C-T

Position:

• chr1-183596965-C-T

Variant summary

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

The XM_047421222.1(NCF2):​c.-143-4399G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.389 in 152,066 control chromosomes in the GnomAD database, including 11,650 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 (11650 hom., cov: 32)
• Consequence: NCF2 XM_047421222.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.572

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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.424 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NCF2	XM_047421222.1	c.-143-4399G>A		intron_variant			XP_047277178.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SMG7	ENST00000495321.1	n.234-804C>T		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.388 AC: 59024 AN: 151948 Hom.: 11625 Cov.: 32

Gnomad AFR AF: 0.429

Gnomad AMI AF: 0.263

Gnomad AMR AF: 0.333

Gnomad ASJ AF: 0.371

Gnomad EAS AF: 0.170

Gnomad SAS AF: 0.333

Gnomad FIN AF: 0.382

Gnomad MID AF: 0.440

Gnomad NFE AF: 0.400

Gnomad OTH AF: 0.385

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

GnomAD4 genome AF: 0.389 AC: 59082 AN: 152066 Hom.: 11650 Cov.: 32 AF XY: 0.384 AC XY: 28569 AN XY: 74318

Gnomad4 AFR AF: 0.430

Gnomad4 AMR AF: 0.332

Gnomad4 ASJ AF: 0.371

Gnomad4 EAS AF: 0.170

Gnomad4 SAS AF: 0.332

Gnomad4 FIN AF: 0.382

Gnomad4 NFE AF: 0.400

Gnomad4 OTH AF: 0.382

Alfa AF: 0.394 Hom.: 3620

Bravo AF: 0.389

Asia WGS AF: 0.262 AC: 911 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.7
DANN	Benign	0.59

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2333686; hg19: chr1-183566100;