ENST00000438382.2:n.368A>G

Variant names:

• chr7-75166663-T-C
• rs13447
• ENST00000438382.2:n.368A>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The ENST00000438382.2(NCF1C):​n.368A>G variant causes a non coding transcript exon change. 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 0.00014 (0 hom., cov: 4)
  • Exomes 𝑓: 0.0024 (49 hom.)
  • Failed GnomAD Quality Control
• Consequence: NCF1C ENST00000438382.2 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.24
• Publications: 7 publications found

Genes affected

NCF1C (HGNC:32523): (neutrophil cytosolic factor 1C (pseudogene)) The neutrophil cytosolic factor 1 (NCF1) gene encodes the 47 kDa cytosolic subunit of neutrophil NADPH oxidase, which produces superoxide anion. The NCF1 gene is located in close proximity to two highly similar, multi-exon pseudogenes at chromosome 7q11.23, corresponding to this gene record and GeneID:654816. The two pseudogenes contain a dinucleotide deletion (delta-GT) in exon 2 that results in a frameshift and truncation of the open reading frame, and neither pseudogene is likely to express a protein. Recombination events between the pseudogenes and the functional NCF1 gene can inactivate the NCF1 gene and result in chronic granulomatous disease. [provided by RefSeq, Nov 2009]

NCF1C (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000438382.2. 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
	NCF1C	NR_003187.3		n.322A>G		non_coding_transcript_exon	Exon 4 of 11

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NCF1C	ENST00000438382.2	TSL:6	n.368A>G		non_coding_transcript_exon	Exon 4 of 11
	NCF1C	ENST00000740088.1		n.326A>G		non_coding_transcript_exon	Exon 4 of 11
	NCF1C	ENST00000740089.1		n.289A>G		non_coding_transcript_exon	Exon 4 of 10

Frequencies

GnomAD3 genomes AF: 0.000142 AC: 6 AN: 42350 Hom.: 0 Cov.: 4

Gnomad AFR AF: 0.000116

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000316

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000183

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0193 AC: 4297 AN: 222814 AF XY: 0.0171

Gnomad AFR exome AF: 0.148

Gnomad AMR exome AF: 0.0139

Gnomad ASJ exome AF: 0.0148

Gnomad EAS exome AF: 0.0138

Gnomad FIN exome AF: 0.0116

Gnomad NFE exome AF: 0.0122

Gnomad OTH exome AF: 0.0211

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00235 AC: 2958 AN: 1257140 Hom.: 49 Cov.: 31 AF XY: 0.00251 AC XY: 1567 AN XY: 624628

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00356 AC: 95 AN: 26686

American (AMR) AF: 0.00382 AC: 150 AN: 39318

Ashkenazi Jewish (ASJ) AF: 0.00514 AC: 98 AN: 19062

East Asian (EAS) AF: 0.00176 AC: 46 AN: 26096

South Asian (SAS) AF: 0.00607 AC: 492 AN: 81046

European-Finnish (FIN) AF: 0.00207 AC: 75 AN: 36182

Middle Eastern (MID) AF: 0.00101 AC: 4 AN: 3952

European-Non Finnish (NFE) AF: 0.00190 AC: 1857 AN: 976060

Other (OTH) AF: 0.00289 AC: 141 AN: 48738

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000141 AC: 6 AN: 42422 Hom.: 0 Cov.: 4 AF XY: 0.000150 AC XY: 3 AN XY: 20040

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000116 AC: 2 AN: 17258

American (AMR) AF: 0.000315 AC: 1 AN: 3172

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 770

East Asian (EAS) AF: 0.00 AC: 0 AN: 1018

South Asian (SAS) AF: 0.00 AC: 0 AN: 1370

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 1628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 116

European-Non Finnish (NFE) AF: 0.000183 AC: 3 AN: 16370

Other (OTH) AF: 0.00 AC: 0 AN: 582

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.0199 Hom.: 45

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	17
DANN	Benign	0.79
PhyloP100		4.2

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs13447;

hg19: chr7-74582468;