rs150638770
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_ModerateBP6BS1
The NM_000079.4(CHRNA1):c.655C>T(p.Leu219=) variant causes a synonymous change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0031 in 1,614,148 control chromosomes in the GnomAD database, including 7 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. L219L) has been classified as Likely benign.
Frequency
Consequence
NM_000079.4 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CHRNA1 | NM_000079.4 | c.655C>T | p.Leu219= | synonymous_variant | 6/9 | ENST00000348749.9 | |
CHRNA1 | NM_001039523.3 | c.730C>T | p.Leu244= | synonymous_variant | 7/10 | ||
CHRNA1 | XM_017003256.2 | c.751C>T | p.Leu251= | synonymous_variant | 6/9 | ||
CHRNA1 | XM_017003257.2 | c.676C>T | p.Leu226= | synonymous_variant | 5/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CHRNA1 | ENST00000348749.9 | c.655C>T | p.Leu219= | synonymous_variant | 6/9 | 1 | NM_000079.4 | P1 | |
ENST00000442996.1 | n.322-19123G>A | intron_variant, non_coding_transcript_variant | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.00208 AC: 317AN: 152136Hom.: 1 Cov.: 31
GnomAD3 exomes AF: 0.00245 AC: 615AN: 251472Hom.: 1 AF XY: 0.00248 AC XY: 337AN XY: 135916
GnomAD4 exome AF: 0.00321 AC: 4693AN: 1461894Hom.: 6 Cov.: 31 AF XY: 0.00315 AC XY: 2291AN XY: 727248
GnomAD4 genome ? AF: 0.00208 AC: 317AN: 152254Hom.: 1 Cov.: 31 AF XY: 0.00183 AC XY: 136AN XY: 74436
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Dec 17, 2014 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jun 01, 2023 | CHRNA1: BP4, BS2 - |
not specified Benign:2
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Mar 24, 2017 | - - |
Lethal multiple pterygium syndrome Benign:2
Likely benign, 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 and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Congenital myasthenic syndrome Benign:1
Likely benign, 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 and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at