chr7-74777567-C-T

Position:

• chr7-74777567-C-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_000265.7(NCF1):​c.153+220C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00818 in 513,954 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0070 (4 hom., cov: 23)
  • Exomes 𝑓: 0.0087 (17 hom.)
• Consequence: NCF1 NM_000265.7 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.43

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 -16 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP6: Variant 7-74777567-C-T is Benign according to our data. Variant chr7-74777567-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1247524.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NCF1	NM_000265.7	c.153+220C>T		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+220C>T		intron_variant		1	NM_000265.7	ENSP00000289473.4

Frequencies

GnomAD3 genomes AF: 0.00700 AC: 1064 AN: 151904 Hom.: 4 Cov.: 23

Gnomad AFR AF: 0.00174

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00151

Gnomad ASJ AF: 0.000865

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00208

Gnomad FIN AF: 0.0191

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0109

Gnomad OTH AF: 0.00527

GnomAD4 exome AF: 0.00867 AC: 3138 AN: 361936 Hom.: 17 Cov.: 5 AF XY: 0.00817 AC XY: 1584 AN XY: 193992

Gnomad4 AFR exome AF: 0.00127

Gnomad4 AMR exome AF: 0.00112

Gnomad4 ASJ exome AF: 0.000728

Gnomad4 EAS exome AF: 0.000187

Gnomad4 SAS exome AF: 0.00224

Gnomad4 FIN exome AF: 0.0193

Gnomad4 NFE exome AF: 0.0107

Gnomad4 OTH exome AF: 0.00606

GnomAD4 genome AF: 0.00700 AC: 1064 AN: 152018 Hom.: 4 Cov.: 23 AF XY: 0.00692 AC XY: 514 AN XY: 74324

Gnomad4 AFR AF: 0.00174

Gnomad4 AMR AF: 0.00151

Gnomad4 ASJ AF: 0.000865

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00208

Gnomad4 FIN AF: 0.0191

Gnomad4 NFE AF: 0.0109

Gnomad4 OTH AF: 0.00522

Alfa AF: 0.00370 Hom.: 0

Bravo AF: 0.00587

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 24, 2021	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	2.4
DANN	Benign	0.78

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

Publications

LitVar

Other links and lift over

dbSNP: rs142050799; hg19: chr7-74191913;