rs746713

Variant names:

• chr22-36863317-T-C
• rs746713
• NM_000631.5:c.33-728T>C

Your query was ambiguous. Multiple possible variants found:

• chr22-36863317-T-C
• chr22-36863317-T-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000631.5(NCF4):​c.33-728T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.305 in 151,564 control chromosomes in the GnomAD database, including 7,127 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 0.31 (7127 hom., cov: 28)
• Consequence: NCF4 NM_000631.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.284
• Publications: 11 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.367 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NCF4	NM_000631.5	c.33-728T>C		intron_variant	Intron 1 of 9	ENST00000248899.11	NP_000622.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NCF4	ENST00000248899.11	c.33-728T>C		intron_variant	Intron 1 of 9	1	NM_000631.5	ENSP00000248899.6

Frequencies

GnomAD3 genomes AF: 0.305 AC: 46225 AN: 151444 Hom.: 7119 Cov.: 28

Gnomad AFR AF: 0.321

Gnomad AMI AF: 0.279

Gnomad AMR AF: 0.244

Gnomad ASJ AF: 0.322

Gnomad EAS AF: 0.322

Gnomad SAS AF: 0.383

Gnomad FIN AF: 0.313

Gnomad MID AF: 0.239

Gnomad NFE AF: 0.302

Gnomad OTH AF: 0.296

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

GnomAD4 genome AF: 0.305 AC: 46256 AN: 151564 Hom.: 7127 Cov.: 28 AF XY: 0.306 AC XY: 22675 AN XY: 73996

African (AFR) AF: 0.321 AC: 13246 AN: 41292

American (AMR) AF: 0.243 AC: 3711 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.322 AC: 1116 AN: 3462

East Asian (EAS) AF: 0.322 AC: 1632 AN: 5070

South Asian (SAS) AF: 0.381 AC: 1826 AN: 4788

European-Finnish (FIN) AF: 0.313 AC: 3290 AN: 10522

Middle Eastern (MID) AF: 0.233 AC: 68 AN: 292

European-Non Finnish (NFE) AF: 0.302 AC: 20477 AN: 67866

Other (OTH) AF: 0.302 AC: 636 AN: 2104

Alfa AF: 0.290 Hom.: 10885

Bravo AF: 0.296

Asia WGS AF: 0.405 AC: 1407 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.9
DANN	Benign	0.75
PhyloP100		-0.28
PromoterAI		-0.023	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs746713; hg19: chr22-37259359;