NM_000166.6:c.-6G>A
Variant summary
Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2
The NM_000166.6(GJB1):c.-6G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00042 in 1,208,773 control chromosomes in the GnomAD database, including 3 homozygotes. There are 173 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Consequence
NM_000166.6 5_prime_UTR
Scores
Clinical Significance
Conservation
Publications
- Charcot-Marie-Tooth disease X-linked dominant 1Inheritance: XL Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, PanelApp Australia, ClinGen, Labcorp Genetics (formerly Invitae)
- X-linked progressive cerebellar ataxiaInheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet
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ACMG classification
Our verdict: Benign. The variant received -12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
GJB1 | NM_000166.6 | c.-6G>A | 5_prime_UTR_variant | Exon 2 of 2 | ENST00000361726.7 | NP_000157.1 | ||
GJB1 | NM_001097642.3 | c.-6G>A | 5_prime_UTR_variant | Exon 2 of 2 | NP_001091111.1 | |||
GJB1 | NM_001440770.1 | c.-6G>A | 5_prime_UTR_variant | Exon 3 of 3 | NP_001427699.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000440 AC: 49AN: 111349Hom.: 0 Cov.: 23 show subpopulations
GnomAD2 exomes AF: 0.000480 AC: 87AN: 181315 AF XY: 0.000450 show subpopulations
GnomAD4 exome AF: 0.000418 AC: 459AN: 1097369Hom.: 3 Cov.: 31 AF XY: 0.000435 AC XY: 158AN XY: 362817 show subpopulations
Age Distribution
GnomAD4 genome AF: 0.000440 AC: 49AN: 111404Hom.: 0 Cov.: 23 AF XY: 0.000446 AC XY: 15AN XY: 33642 show subpopulations
Age Distribution
ClinVar
Submissions by phenotype
not provided Benign:2
GJB1: BP4, BS2 -
See Variant Classification Assertion Criteria. -
Charcot-Marie-Tooth disease Benign:1
- -
not specified Benign:1
- -
Charcot-Marie-Tooth disease X-linked dominant 1 Benign:1
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 and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at