rs56026241
Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1
The NM_001164508.2(NEB):c.21418-6delA variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).
Frequency
Consequence
NM_001164508.2 splice_region, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -16 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
NEB | NM_001164507.2 | c.21418-6delA | splice_region_variant, intron_variant | Intron 143 of 181 | ENST00000427231.7 | NP_001157979.2 | ||
NEB | NM_001164508.2 | c.21418-6delA | splice_region_variant, intron_variant | Intron 143 of 181 | ENST00000397345.8 | NP_001157980.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
NEB | ENST00000397345.8 | c.21418-6delA | splice_region_variant, intron_variant | Intron 143 of 181 | 5 | NM_001164508.2 | ENSP00000380505.3 | |||
NEB | ENST00000427231.7 | c.21418-6delA | splice_region_variant, intron_variant | Intron 143 of 181 | 5 | NM_001164507.2 | ENSP00000416578.2 |
Frequencies
GnomAD3 genomes AF: 0.554 AC: 84079AN: 151834Hom.: 24334 Cov.: 0
GnomAD3 exomes AF: 0.591 AC: 127200AN: 215382Hom.: 38523 AF XY: 0.581 AC XY: 67119AN XY: 115620
GnomAD4 exome AF: 0.607 AC: 858614AN: 1414682Hom.: 264503 Cov.: 0 AF XY: 0.601 AC XY: 422334AN XY: 702968
GnomAD4 genome AF: 0.554 AC: 84129AN: 151952Hom.: 24355 Cov.: 0 AF XY: 0.556 AC XY: 41269AN XY: 74260
ClinVar
Submissions by phenotype
not specified Benign:3
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: c.21523-6dupA in NEB gene is an intronic change that involves a mildly conserved nucleotide. 3/5 programs in Alamut predict that this variant does not have significant effect on the normal splicing pattern, however no functional studies supporting this notion were published at the time of evaluation. The variant is present in the control population dataset of ExAC at a frequency of 0.6045 (49666 /82164chrs tested), including numerous homozygotes across multiple populations. The observed frequency exceed the maximum expected allele frequency for a pathogenic variant of 0.0035. The variant of interest has not, to our knowledge, been reported in affected individuals in published reports but cited as Benign by reputable databases/clinical laboratories. Considering all, the variant was classified as Benign. -
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Nemaline myopathy 2 Benign:2
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Nemaline Myopathy, Recessive Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at