rs707410

Positions:

• chr7-74777361-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000289473.11(NCF1):​c.153+14T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.814 in 1,450,804 control chromosomes in the GnomAD database, including 478,478 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.83 (45850 hom., cov: 18)
  • Exomes 𝑓: 0.81 (432628 hom.)
• Consequence: NCF1 ENST00000289473.11 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -4.88

Genes affected

NCF1 (HGNC:7660): (neutrophil cytosolic factor 1) The protein encoded by this gene is a 47 kDa cytosolic subunit of neutrophil NADPH oxidase. This oxidase is a multicomponent enzyme that is activated to produce superoxide anion. Mutations in this gene have been associated with chronic granulomatous disease. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 7-74777361-T-C is Benign according to our data. Variant chr7-74777361-T-C is described in ClinVar as [Benign]. Clinvar id is 1685959.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.932 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NCF1	NM_000265.7	c.153+14T>C		intron_variant		ENST00000289473.11	NP_000256.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NCF1	ENST00000289473.11	c.153+14T>C		intron_variant		1	NM_000265.7	ENSP00000289473	P1

Frequencies

GnomAD3 genomes AF: 0.827 AC: 111762 AN: 135148 Hom.: 45812 Cov.: 18

Gnomad AFR AF: 0.876

Gnomad AMI AF: 0.845

Gnomad AMR AF: 0.837

Gnomad ASJ AF: 0.810

Gnomad EAS AF: 0.957

Gnomad SAS AF: 0.835

Gnomad FIN AF: 0.820

Gnomad MID AF: 0.829

Gnomad NFE AF: 0.789

Gnomad OTH AF: 0.828

GnomAD4 exome AF: 0.813 AC: 1069805 AN: 1315548 Hom.: 432628 Cov.: 25 AF XY: 0.814 AC XY: 535504 AN XY: 657520

Gnomad4 AFR exome AF: 0.888

Gnomad4 AMR exome AF: 0.868

Gnomad4 ASJ exome AF: 0.813

Gnomad4 EAS exome AF: 0.955

Gnomad4 SAS exome AF: 0.844

Gnomad4 FIN exome AF: 0.830

Gnomad4 NFE exome AF: 0.799

Gnomad4 OTH exome AF: 0.822

GnomAD4 genome AF: 0.827 AC: 111849 AN: 135256 Hom.: 45850 Cov.: 18 AF XY: 0.826 AC XY: 53895 AN XY: 65248

Gnomad4 AFR AF: 0.876

Gnomad4 AMR AF: 0.838

Gnomad4 ASJ AF: 0.810

Gnomad4 EAS AF: 0.957

Gnomad4 SAS AF: 0.836

Gnomad4 FIN AF: 0.820

Gnomad4 NFE AF: 0.789

Gnomad4 OTH AF: 0.828

Alfa AF: 0.815 Hom.: 8309

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan	Jan 24, 2024	This variant is classified as Benign based on local population frequency. This variant was detected in 92% of patients studied by a panel of primary immunodeficiencies. Number of patients: 87. Only high quality variants are reported. -
Benign, criteria provided, single submitter	clinical testing	Mendelics	May 04, 2022	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.0020

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs707410; hg19: chr7-74191707;