rs760519

Variant names:

• chr22-36867664-C-T
• rs760519
• NM_000631.5:c.342+202C>T

Your query was ambiguous. Multiple possible variants found:

• chr22-36867664-C-T
• chr22-36867664-C-G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000631.5(NCF4):​c.342+202C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.846 in 152,176 control chromosomes in the GnomAD database, including 54,588 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.85 (54588 hom., cov: 32)
• Consequence: NCF4 NM_000631.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.11
• Publications: 23 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BP6: Variant 22-36867664-C-T is Benign according to our data. Variant chr22-36867664-C-T is described in ClinVar as Benign. ClinVar VariationId is 1230820.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.891 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000631.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NCF4	NM_000631.5	MANE Select	c.342+202C>T		intron	N/A	NP_000622.2
	NCF4	NM_013416.4		c.342+202C>T		intron	N/A	NP_038202.2	Q15080-3
	NCF4-AS1	NR_147197.1		n.351+2429G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NCF4	ENST00000248899.11	TSL:1 MANE Select	c.342+202C>T		intron	N/A	ENSP00000248899.6	Q15080-1
	NCF4	ENST00000397147.7	TSL:1	c.342+202C>T		intron	N/A	ENSP00000380334.4	Q15080-3
	NCF4	ENST00000650698.1		c.33+202C>T		intron	N/A	ENSP00000498381.1	A0A494BZS1

Frequencies

GnomAD3 genomes AF: 0.846 AC: 128609 AN: 152058 Hom.: 54545 Cov.: 32

Gnomad AFR AF: 0.899

Gnomad AMI AF: 0.770

Gnomad AMR AF: 0.859

Gnomad ASJ AF: 0.864

Gnomad EAS AF: 0.685

Gnomad SAS AF: 0.797

Gnomad FIN AF: 0.819

Gnomad MID AF: 0.791

Gnomad NFE AF: 0.831

Gnomad OTH AF: 0.841

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

GnomAD4 genome AF: 0.846 AC: 128708 AN: 152176 Hom.: 54588 Cov.: 32 AF XY: 0.844 AC XY: 62776 AN XY: 74384

African (AFR) AF: 0.899 AC: 37330 AN: 41524

American (AMR) AF: 0.859 AC: 13143 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.864 AC: 2999 AN: 3472

East Asian (EAS) AF: 0.685 AC: 3527 AN: 5150

South Asian (SAS) AF: 0.797 AC: 3845 AN: 4826

European-Finnish (FIN) AF: 0.819 AC: 8673 AN: 10592

Middle Eastern (MID) AF: 0.803 AC: 236 AN: 294

European-Non Finnish (NFE) AF: 0.831 AC: 56480 AN: 68004

Other (OTH) AF: 0.840 AC: 1774 AN: 2112

Alfa AF: 0.837 Hom.: 109285

Bravo AF: 0.850

Asia WGS AF: 0.800 AC: 2782 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.23
DANN	Benign	0.70
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs760519; hg19: chr22-37263706;