chr22-36875840-T-C
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The ENST00000397147.7(NCF4):c.815T>C(p.Leu272Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.831 in 1,614,022 control chromosomes in the GnomAD database, including 558,514 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L272Q) has been classified as Benign.
Frequency
Consequence
ENST00000397147.7 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NCF4 | NM_000631.5 | c.758+57T>C | intron_variant | ENST00000248899.11 | |||
NCF4 | NM_013416.4 | c.815T>C | p.Leu272Pro | missense_variant | 8/9 | ||
NCF4 | XM_047441384.1 | c.932+57T>C | intron_variant | ||||
NCF4 | XM_047441385.1 | c.902+57T>C | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NCF4 | ENST00000248899.11 | c.758+57T>C | intron_variant | 1 | NM_000631.5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.861 AC: 130923AN: 152054Hom.: 56674 Cov.: 31
GnomAD3 exomes AF: 0.831 AC: 208985AN: 251444Hom.: 87262 AF XY: 0.828 AC XY: 112576AN XY: 135894
GnomAD4 exome AF: 0.828 AC: 1210107AN: 1461850Hom.: 501774 Cov.: 85 AF XY: 0.828 AC XY: 601888AN XY: 727228
GnomAD4 genome AF: 0.861 AC: 131046AN: 152172Hom.: 56740 Cov.: 31 AF XY: 0.859 AC XY: 63932AN XY: 74386
ClinVar
Submissions by phenotype
not specified Benign:3
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 96% of patients studied by a panel of primary immunodeficiencies. Number of patients: 91. Only high quality variants are reported. - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Mar 28, 2016 | Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency - |
Granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type 3 Benign:2
Benign, criteria provided, single submitter | clinical testing | Mendelics | May 28, 2019 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
not provided Benign:1Other:1
not provided, no classification provided | phenotyping only | GenomeConnect, ClinGen | - | Variant interpreted as Benign and reported on 04-27-2020 by Lab or GTR ID 500031. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. This variant was reported in an individual referred for clinical diagnostic genetic testing. - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Sep 05, 2018 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at