rs707410

Variant names:

• chr7-74777361-T-C
• rs707410
• NM_000265.7:c.153+14T>C

Variant summary

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

The NM_000265.7(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 NM_000265.7 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 rank	MANE	Protein	UniProt
NCF1	NM_000265.7	c.153+14T>C		intron_variant	Intron 2 of 10	ENST00000289473.11	NP_000256.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NCF1	ENST00000289473.11	c.153+14T>C		intron_variant	Intron 2 of 10	1	NM_000265.7	ENSP00000289473.4

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

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

May 04, 2022

Mendelics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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;