chr2-151485796-G-A
Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2
The NM_001164508.2(NEB):c.25542C>T(p.Thr8514Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00169 in 1,612,818 control chromosomes in the GnomAD database, including 41 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Consequence
NM_001164508.2 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -19 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
NEB | ENST00000397345.8 | c.25542C>T | p.Thr8514Thr | synonymous_variant | Exon 182 of 182 | 5 | NM_001164508.2 | ENSP00000380505.3 | ||
NEB | ENST00000427231.7 | c.25542C>T | p.Thr8514Thr | synonymous_variant | Exon 182 of 182 | 5 | NM_001164507.2 | ENSP00000416578.2 |
Frequencies
GnomAD3 genomes AF: 0.00239 AC: 364AN: 152146Hom.: 9 Cov.: 32
GnomAD3 exomes AF: 0.00543 AC: 1348AN: 248224Hom.: 24 AF XY: 0.00503 AC XY: 677AN XY: 134546
GnomAD4 exome AF: 0.00161 AC: 2357AN: 1460554Hom.: 32 Cov.: 31 AF XY: 0.00154 AC XY: 1122AN XY: 726380
GnomAD4 genome AF: 0.00237 AC: 361AN: 152264Hom.: 9 Cov.: 32 AF XY: 0.00250 AC XY: 186AN XY: 74454
ClinVar
Submissions by phenotype
not specified Benign:3
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This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
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not provided Benign:2
Variant summary: The c.25647C>T (p.Thr8549=) in NEB gene is a synonymous change that involves a non-conserved nucleotide. 5/5 programs in Alamut predict that this variant does not affect a normal splicing, however no functional studies supporting this notion were published at the time of evaluation. The variant is present in control population dataset of ExAC at a frequency of 0.0049 (593/120504 chrs tested), predominantly in individuals of East Asian descent (0.047; 403/8622chrs tested, including 12 homozygotes). These frequencies exceed the estimated maximal expected allele frequency of a pathogenic variant in NEB gene (0.0035). Lastly, multiple reputable databases/diagnostic centers classified the variant of interest as Benign. Taking together, the variant was classified as Benign. -
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Nemaline myopathy 2 Benign:2
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This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at