rs34567417

Variant names:

• chr22-36861135-G-A
• rs34567417
• NM_000631.5:c.-37G>A

Your query was ambiguous. Multiple possible variants found:

• chr22-36861135-G-A
• chr22-36861135-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000631.5(NCF4):​c.-37G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0639 in 1,550,882 control chromosomes in the GnomAD database, including 3,604 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.049 (264 hom., cov: 32)
  • Exomes 𝑓: 0.066 (3340 hom.)
• Consequence: NCF4 NM_000631.5 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.58
• Publications: 4 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 22-36861135-G-A is Benign according to our data. Variant chr22-36861135-G-A is described in ClinVar as [Benign]. Clinvar id is 1265734.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0904 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NCF4	NM_000631.5	c.-37G>A		5_prime_UTR_variant	Exon 1 of 10	ENST00000248899.11	NP_000622.2
NCF4	NM_013416.4	c.-37G>A		5_prime_UTR_variant	Exon 1 of 9		NP_038202.2
NCF4-AS1	NR_147197.1	n.351+8958C>T		intron_variant	Intron 1 of 1
NCF4	XM_047441385.1	c.-584G>A		upstream_gene_variant			XP_047297341.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NCF4	ENST00000248899.11	c.-37G>A		5_prime_UTR_variant	Exon 1 of 10	1	NM_000631.5	ENSP00000248899.6

Frequencies

GnomAD3 genomes AF: 0.0486 AC: 7398 AN: 152148 Hom.: 264 Cov.: 32

Gnomad AFR AF: 0.0132

Gnomad AMI AF: 0.134

Gnomad AMR AF: 0.0512

Gnomad ASJ AF: 0.0424

Gnomad EAS AF: 0.0608

Gnomad SAS AF: 0.0972

Gnomad FIN AF: 0.0251

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0674

Gnomad OTH AF: 0.0659

GnomAD2 exomes AF: 0.0579 AC: 8909 AN: 153950 AF XY: 0.0626

Gnomad AFR exome AF: 0.0111

Gnomad AMR exome AF: 0.0364

Gnomad ASJ exome AF: 0.0463

Gnomad EAS exome AF: 0.0557

Gnomad FIN exome AF: 0.0257

Gnomad NFE exome AF: 0.0706

Gnomad OTH exome AF: 0.0703

GnomAD4 exome AF: 0.0656 AC: 91732 AN: 1398616 Hom.: 3340 Cov.: 31 AF XY: 0.0666 AC XY: 45957 AN XY: 689846

African (AFR) AF: 0.0104 AC: 330 AN: 31584

American (AMR) AF: 0.0396 AC: 1415 AN: 35698

Ashkenazi Jewish (ASJ) AF: 0.0468 AC: 1178 AN: 25168

East Asian (EAS) AF: 0.0571 AC: 2041 AN: 35742

South Asian (SAS) AF: 0.0910 AC: 7206 AN: 79206

European-Finnish (FIN) AF: 0.0274 AC: 1351 AN: 49218

Middle Eastern (MID) AF: 0.0781 AC: 438 AN: 5606

European-Non Finnish (NFE) AF: 0.0685 AC: 73921 AN: 1078432

Other (OTH) AF: 0.0665 AC: 3852 AN: 57962

GnomAD4 genome AF: 0.0486 AC: 7406 AN: 152266 Hom.: 264 Cov.: 32 AF XY: 0.0481 AC XY: 3579 AN XY: 74452

African (AFR) AF: 0.0132 AC: 548 AN: 41556

American (AMR) AF: 0.0512 AC: 784 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0424 AC: 147 AN: 3466

East Asian (EAS) AF: 0.0607 AC: 314 AN: 5170

South Asian (SAS) AF: 0.0977 AC: 472 AN: 4830

European-Finnish (FIN) AF: 0.0251 AC: 267 AN: 10626

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.0674 AC: 4584 AN: 67996

Other (OTH) AF: 0.0681 AC: 144 AN: 2116

Alfa AF: 0.0347 Hom.: 39

Bravo AF: 0.0488

Asia WGS AF: 0.0770 AC: 268 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Oct 24, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	17
DANN	Benign	0.90
PhyloP100		-1.6
PromoterAI		-0.011	Neutral
Mutation Taster		=300/0	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: rs34567417; hg19: chr22-37257177; COSMIC: COSV50622132;