rs375340441
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 1P and 9B. PP3BP6BS1BS2
The ENST00000370263.9(CHRNA4):āc.961A>Gā(p.Ile321Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000496 in 1,613,262 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. I321I) has been classified as Likely benign.
Frequency
Consequence
ENST00000370263.9 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CHRNA4 | NM_000744.7 | c.961A>G | p.Ile321Val | missense_variant | 5/6 | ENST00000370263.9 | NP_000735.1 | |
CHRNA4 | NM_001256573.2 | c.433A>G | p.Ile145Val | missense_variant | 5/6 | NP_001243502.1 | ||
CHRNA4 | NR_046317.2 | n.1170A>G | non_coding_transcript_exon_variant | 5/6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CHRNA4 | ENST00000370263.9 | c.961A>G | p.Ile321Val | missense_variant | 5/6 | 1 | NM_000744.7 | ENSP00000359285 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000198 AC: 3AN: 151594Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000399 AC: 1AN: 250932Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135864
GnomAD4 exome AF: 0.00000342 AC: 5AN: 1461668Hom.: 0 Cov.: 99 AF XY: 0.00000413 AC XY: 3AN XY: 727118
GnomAD4 genome AF: 0.0000198 AC: 3AN: 151594Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 73974
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | May 20, 2024 | The c.961A>G (p.I321V) alteration is located in exon 5 (coding exon 5) of the CHRNA4 gene. This alteration results from a A to G substitution at nucleotide position 961, causing the isoleucine (I) at amino acid position 321 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Oct 25, 2019 | Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Autosomal dominant nocturnal frontal lobe epilepsy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Dec 16, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at