rs2333686

Variant names:

• chr1-183596965-C-T
• rs2333686
• ENST00000495321.1:n.234-804C>T

Variant summary

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

The ENST00000495321.1(SMG7):​n.234-804C>T 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: SMG7 ENST00000495321.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.572
• Publications: 11 publications found

Genes affected

SMG7 (HGNC:16792): (SMG7 nonsense mediated mRNA decay factor) This gene encodes a protein that is essential for nonsense-mediated mRNA decay (NMD); a process whereby transcripts with premature termination codons are targeted for rapid degradation by a mRNA decay complex. The mRNA decay complex consists, in part, of this protein along with proteins SMG5 and UPF1. The N-terminal domain of this protein is thought to mediate its association with SMG5 or UPF1 while the C-terminal domain interacts with the mRNA decay complex. This protein may therefore couple changes in UPF1 phosphorylation state to the degradation of NMD-candidate transcripts. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Aug 2011]

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]

NCF2 Gene-Disease associations (from GenCC):

• granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type 2

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• chronic granulomatous disease

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
NCF2	XM_047421222.1	c.-143-4399G>A		intron_variant	Intron 1 of 16		XP_047277178.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMG7	ENST00000495321.1	n.234-804C>T		intron_variant	Intron 2 of 3	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

African (AFR) AF: 0.430 AC: 17804 AN: 41452

American (AMR) AF: 0.332 AC: 5080 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.371 AC: 1289 AN: 3470

East Asian (EAS) AF: 0.170 AC: 883 AN: 5188

South Asian (SAS) AF: 0.332 AC: 1600 AN: 4822

European-Finnish (FIN) AF: 0.382 AC: 4035 AN: 10556

Middle Eastern (MID) AF: 0.442 AC: 130 AN: 294

European-Non Finnish (NFE) AF: 0.400 AC: 27215 AN: 67974

Other (OTH) AF: 0.382 AC: 807 AN: 2114

Alfa AF: 0.398 Hom.: 6137

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
PhyloP100		0.57

Splicing

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

Other links and lift over

dbSNP: rs2333686; hg19: chr1-183566100;