7-74779322-A-G

Position:

• chr7-74779322-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000265.7(NCF1):​c.295A>G​(p.Ser99Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 1,400,968 control chromosomes in the GnomAD database, including 13,412 homozygotes. In-silico tool predicts a benign outcome for this variant. 5/6 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.17 (1794 hom., cov: 22)
  • Exomes 𝑓: 0.11 (13412 hom.)
  • Failed GnomAD Quality Control
• Consequence: NCF1 NM_000265.7 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.480

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.001658678).
• BP6: Variant 7-74779322-A-G is Benign according to our data. Variant chr7-74779322-A-G is described in ClinVar as [Benign]. Clinvar id is 2786565.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr7-74779322-A-G is described in Lovd as [Benign].
• BA1: GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.271 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NCF1	NM_000265.7	c.295A>G	p.Ser99Gly	missense_variant	4/11	ENST00000289473.11	NP_000256.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NCF1	ENST00000289473.11	c.295A>G	p.Ser99Gly	missense_variant	4/11	1	NM_000265.7	ENSP00000289473.4

Frequencies

GnomAD3 genomes AF: 0.171 AC: 23536 AN: 137296 Hom.: 1788 Cov.: 22

Gnomad AFR AF: 0.294

Gnomad AMI AF: 0.259

Gnomad AMR AF: 0.180

Gnomad ASJ AF: 0.113

Gnomad EAS AF: 0.134

Gnomad SAS AF: 0.116

Gnomad FIN AF: 0.153

Gnomad MID AF: 0.175

Gnomad NFE AF: 0.118

Gnomad OTH AF: 0.181

GnomAD4 exome AF: 0.114 AC: 159768 AN: 1400968 Hom.: 13412 Cov.: 32 AF XY: 0.114 AC XY: 79430 AN XY: 697546

Gnomad4 AFR exome AF: 0.276

Gnomad4 AMR exome AF: 0.137

Gnomad4 ASJ exome AF: 0.0966

Gnomad4 EAS exome AF: 0.144

Gnomad4 SAS exome AF: 0.120

Gnomad4 FIN exome AF: 0.145

Gnomad4 NFE exome AF: 0.105

Gnomad4 OTH exome AF: 0.135

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.172 AC: 23572 AN: 137406 Hom.: 1794 Cov.: 22 AF XY: 0.173 AC XY: 11572 AN XY: 66968

Gnomad4 AFR AF: 0.294

Gnomad4 AMR AF: 0.179

Gnomad4 ASJ AF: 0.113

Gnomad4 EAS AF: 0.134

Gnomad4 SAS AF: 0.116

Gnomad4 FIN AF: 0.153

Gnomad4 NFE AF: 0.118

Gnomad4 OTH AF: 0.180

Alfa AF: 0.183 Hom.: 465

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.066
BayesDel_noAF	Benign	-0.96
CADD	Benign	3.0
LIST_S2	Benign	0.48	T
MetaRNN	Benign	0.0017	T
Sift4G	Benign	0.52	T
Vest4		0.19
gMVP		0.17

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10614; hg19: chr7-74193668;