chr11-9845619-T-A
Variant summary
Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP6BS1
The NM_030962.4(SBF2):c.3056A>T(p.Gln1019Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000886 in 1,614,010 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. Q1019Q) has been classified as Likely benign.
Frequency
Consequence
NM_030962.4 missense
Scores
Clinical Significance
Conservation
Publications
- Charcot-Marie-Tooth disease type 4B2Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), G2P, ClinGen, Ambry Genetics
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ACMG classification
Our verdict: Benign. The variant received -9 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000118 AC: 18AN: 152226Hom.: 0 Cov.: 32 show subpopulations
GnomAD2 exomes AF: 0.000322 AC: 81AN: 251300 AF XY: 0.000309 show subpopulations
GnomAD4 exome AF: 0.0000855 AC: 125AN: 1461666Hom.: 1 Cov.: 31 AF XY: 0.0000756 AC XY: 55AN XY: 727138 show subpopulations
Age Distribution
GnomAD4 genome AF: 0.000118 AC: 18AN: 152344Hom.: 0 Cov.: 32 AF XY: 0.000148 AC XY: 11AN XY: 74506 show subpopulations
Age Distribution
ClinVar
Submissions by phenotype
not specified Uncertain:1
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not provided Uncertain:1
Reported previously as a variant of uncertain significance in patients with Charcot-Marie-Tooth disease; however, no further information was provided (PMID: 34255403); In silico analysis indicates that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 38439105, 34255403) -
Inborn genetic diseases Benign:1
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -
SBF2-related disorder Benign:1
This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
Charcot-Marie-Tooth disease type 4 Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at