chr7-76302914-G-C
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM1BP4_ModerateBS2
The NM_001540.5(HSPB1):āc.202G>Cā(p.Val68Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000181 in 1,545,538 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ). Synonymous variant affecting the same amino acid position (i.e. V68V) has been classified as Likely benign.
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
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HSPB1 | NM_001540.5 | c.202G>C | p.Val68Leu | missense_variant | 1/3 | ENST00000248553.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HSPB1 | ENST00000248553.7 | c.202G>C | p.Val68Leu | missense_variant | 1/3 | 1 | NM_001540.5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152048Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000684 AC: 1AN: 146276Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 80430
GnomAD4 exome AF: 0.0000172 AC: 24AN: 1393490Hom.: 0 Cov.: 31 AF XY: 0.0000102 AC XY: 7AN XY: 688608
GnomAD4 genome AF: 0.0000263 AC: 4AN: 152048Hom.: 0 Cov.: 33 AF XY: 0.0000404 AC XY: 3AN XY: 74262
ClinVar
Submissions by phenotype
Charcot-Marie-Tooth disease axonal type 2F Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Mar 18, 2022 | Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The leucine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. ClinVar contains an entry for this variant (Variation ID: 410716). This variant has not been reported in the literature in individuals affected with HSPB1-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.002%). This sequence change replaces valine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 68 of the HSPB1 protein (p.Val68Leu). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at