rs201684605
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6BS2_Supporting
The NM_001164507.2(NEB):c.20466+7G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000673 in 1,607,464 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_001164507.2 splice_region, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NEB | NM_001164507.2 | c.20466+7G>A | splice_region_variant, intron_variant | ENST00000427231.7 | |||
NEB | NM_001164508.2 | c.20466+7G>A | splice_region_variant, intron_variant | ENST00000397345.8 | |||
LOC124906081 | XR_007087266.1 | n.5990-982C>T | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NEB | ENST00000397345.8 | c.20466+7G>A | splice_region_variant, intron_variant | 5 | NM_001164508.2 | P5 | |||
NEB | ENST00000427231.7 | c.20466+7G>A | splice_region_variant, intron_variant | 5 | NM_001164507.2 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.000388 AC: 59AN: 152136Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000582 AC: 143AN: 245564Hom.: 1 AF XY: 0.000638 AC XY: 85AN XY: 133148
GnomAD4 exome AF: 0.000703 AC: 1023AN: 1455210Hom.: 2 Cov.: 30 AF XY: 0.000707 AC XY: 512AN XY: 723956
GnomAD4 genome ? AF: 0.000388 AC: 59AN: 152254Hom.: 0 Cov.: 32 AF XY: 0.000430 AC XY: 32AN XY: 74448
ClinVar
Submissions by phenotype
Nemaline myopathy 2 Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | 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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | May 13, 2016 | 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. - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jan 01, 2024 | NEB: BP4 - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at