rs741997

Positions:

• chr22-36862771-A-G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The ENST00000248899.11(NCF4):​c.33-1274A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.101 in 152,272 control chromosomes in the GnomAD database, including 983 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 0.10 (983 hom., cov: 33)
• Consequence: NCF4 ENST00000248899.11 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.328

Genes affected

NCF4 (HGNC:7662): (neutrophil cytosolic factor 4) The protein encoded by this gene is a cytosolic regulatory component of the superoxide-producing phagocyte NADPH-oxidase, a multicomponent enzyme system important for host defense. This protein is preferentially expressed in cells of myeloid lineage. It interacts primarily with neutrophil cytosolic factor 2 (NCF2/p67-phox) to form a complex with neutrophil cytosolic factor 1 (NCF1/p47-phox), which further interacts with the small G protein RAC1 and translocates to the membrane upon cell stimulation. This complex then activates flavocytochrome b, the membrane-integrated catalytic core of the enzyme system. The PX domain of this protein can bind phospholipid products of the PI(3) kinase, which suggests its role in PI(3) kinase-mediated signaling events. The phosphorylation of this protein was found to negatively regulate the enzyme activity. Alternatively spliced transcript variants encoding distinct isoforms have been observed. [provided by RefSeq, Jul 2008]

NCF4-AS1 (HGNC:40393): (NCF4 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.166 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NCF4	NM_000631.5	c.33-1274A>G		intron_variant		ENST00000248899.11	NP_000622.2
NCF4-AS1	NR_147197.1	n.351+7322T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NCF4	ENST00000248899.11	c.33-1274A>G		intron_variant		1	NM_000631.5	ENSP00000248899	P1
NCF4-AS1	ENST00000619915.1	n.349+7322T>C		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.101 AC: 15408 AN: 152154 Hom.: 982 Cov.: 33

Gnomad AFR AF: 0.169

Gnomad AMI AF: 0.117

Gnomad AMR AF: 0.111

Gnomad ASJ AF: 0.127

Gnomad EAS AF: 0.0743

Gnomad SAS AF: 0.0902

Gnomad FIN AF: 0.0453

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.0672

Gnomad OTH AF: 0.119

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

GnomAD4 genome AF: 0.101 AC: 15417 AN: 152272 Hom.: 983 Cov.: 33 AF XY: 0.100 AC XY: 7448 AN XY: 74458

Gnomad4 AFR AF: 0.169

Gnomad4 AMR AF: 0.111

Gnomad4 ASJ AF: 0.127

Gnomad4 EAS AF: 0.0741

Gnomad4 SAS AF: 0.0894

Gnomad4 FIN AF: 0.0453

Gnomad4 NFE AF: 0.0672

Gnomad4 OTH AF: 0.119

Alfa AF: 0.0800 Hom.: 280

Bravo AF: 0.108

Asia WGS AF: 0.103 AC: 357 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	1.8
DANN	Benign	0.67

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.24		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.24		Position offset: 10

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

Publications

LitVar

Other links and lift over

dbSNP: rs741997; hg19: chr22-37258813;