7-76302989-G-A
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM1BP4BP6BS2
The NM_001540.5(HSPB1):c.277G>A(p.Asp93Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000389 in 1,543,046 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_001540.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000460 AC: 7AN: 152208Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000876 AC: 13AN: 148452Hom.: 0 AF XY: 0.0000862 AC XY: 7AN XY: 81188
GnomAD4 exome AF: 0.0000381 AC: 53AN: 1390838Hom.: 0 Cov.: 31 AF XY: 0.0000320 AC XY: 22AN XY: 686874
GnomAD4 genome AF: 0.0000460 AC: 7AN: 152208Hom.: 0 Cov.: 33 AF XY: 0.0000538 AC XY: 4AN XY: 74352
ClinVar
Submissions by phenotype
Charcot-Marie-Tooth disease Uncertain:1
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not provided Uncertain:1
A variant of uncertain significance has been identified in the HSPB1 gene. The D93N variant has been reported previously as a variant of unknown significance in association with CMT; however, additional clinical information and inheritance pattern were not provided (DiVincenzo et al., 2014). The D93N variant is observed in 3/5180 (0.06%) alleles from individuals of European non-Finnish background (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The D93N variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position where amino acids with similar properties to Aspartic acid are tolerated across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant. -
Charcot-Marie-Tooth disease axonal type 2F Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at