rs707410

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 publications found

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]

NCF1 Gene-Disease associations (from GenCC):

• granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type 1

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• chronic granulomatous disease

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000265.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NCF1	NM_000265.7	MANE Select	c.153+14T>C		intron	N/A	NP_000256.4

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NCF1	ENST00000289473.11	TSL:1 MANE Select	c.153+14T>C		intron	N/A	ENSP00000289473.4
	NCF1	ENST00000398421.6	TSL:2	n.188T>C		non_coding_transcript_exon	Exon 2 of 9
	NCF1	ENST00000433458.5	TSL:5	c.78+14T>C		intron	N/A	ENSP00000392870.2

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

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

African (AFR) AF: 0.888 AC: 27251 AN: 30690

American (AMR) AF: 0.868 AC: 36214 AN: 41712

Ashkenazi Jewish (ASJ) AF: 0.813 AC: 19458 AN: 23944

East Asian (EAS) AF: 0.955 AC: 35196 AN: 36872

South Asian (SAS) AF: 0.844 AC: 67912 AN: 80482

European-Finnish (FIN) AF: 0.830 AC: 41901 AN: 50510

Middle Eastern (MID) AF: 0.827 AC: 4341 AN: 5252

European-Non Finnish (NFE) AF: 0.799 AC: 792567 AN: 991378

Other (OTH) AF: 0.822 AC: 44965 AN: 54708

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

African (AFR) AF: 0.876 AC: 31514 AN: 35964

American (AMR) AF: 0.838 AC: 11075 AN: 13222

Ashkenazi Jewish (ASJ) AF: 0.810 AC: 2589 AN: 3196

East Asian (EAS) AF: 0.957 AC: 3976 AN: 4154

South Asian (SAS) AF: 0.836 AC: 3360 AN: 4020

European-Finnish (FIN) AF: 0.820 AC: 7583 AN: 9246

Middle Eastern (MID) AF: 0.822 AC: 212 AN: 258

European-Non Finnish (NFE) AF: 0.789 AC: 49339 AN: 62554

Other (OTH) AF: 0.828 AC: 1493 AN: 1804

Alfa AF: 0.815 Hom.: 8309

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not specified (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.0020
PhyloP100		-4.9
PromoterAI		0.013	Neutral

Splicing

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

Other links and lift over

dbSNP: rs707410; hg19: chr7-74191707;