1-115286622-C-T
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Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6BP7
The NM_002506.3(NGF):c.174G>A(p.Ala58=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000266 in 1,614,236 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000027 ( 1 hom. )
Consequence
NGF
NM_002506.3 synonymous
NM_002506.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.854
Genes affected
NGF (HGNC:7808): (nerve growth factor) This gene is a member of the NGF-beta family and encodes a secreted protein which homodimerizes and is incorporated into a larger complex. This protein has nerve growth stimulating activity and the complex is involved in the regulation of growth and the differentiation of sympathetic and certain sensory neurons. Mutations in this gene have been associated with hereditary sensory and autonomic neuropathy, type 5 (HSAN5), and dysregulation of this gene's expression is associated with allergic rhinitis. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.81).
BP6
Variant 1-115286622-C-T is Benign according to our data. Variant chr1-115286622-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 526751.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=2, Uncertain_significance=1}.
BP7
Synonymous conserved (PhyloP=-0.854 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NGF | NM_002506.3 | c.174G>A | p.Ala58= | synonymous_variant | 3/3 | ENST00000369512.3 | |
NGF-AS1 | NR_157569.1 | n.207+3382C>T | intron_variant, non_coding_transcript_variant | ||||
NGF | XM_011541518.3 | c.339G>A | p.Ala113= | synonymous_variant | 3/3 | ||
NGF | XM_006710663.4 | c.174G>A | p.Ala58= | synonymous_variant | 2/2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NGF | ENST00000369512.3 | c.174G>A | p.Ala58= | synonymous_variant | 3/3 | 1 | NM_002506.3 | P1 | |
NGF-AS1 | ENST00000425449.1 | n.207+3382C>T | intron_variant, non_coding_transcript_variant | 2 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152238Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251374Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135898
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GnomAD4 exome AF: 0.0000274 AC: 40AN: 1461880Hom.: 1 Cov.: 30 AF XY: 0.0000303 AC XY: 22AN XY: 727246
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GnomAD4 genome AF: 0.0000197 AC: 3AN: 152356Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74496
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:2
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Congenital sensory neuropathy with selective loss of small myelinated fibers Uncertain:1Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Aug 10, 2022 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. - |
NGF-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Mar 18, 2019 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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BayesDel_noAF
Benign
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DANN
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at