rs1044396
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_000744.7(CHRNA4):c.1629C>T(p.Ser543Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.512 in 1,609,060 control chromosomes in the GnomAD database, including 220,241 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Consequence
NM_000744.7 synonymous
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Benign. Variant got -21 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CHRNA4 | NM_000744.7 | c.1629C>T | p.Ser543Ser | synonymous_variant | Exon 5 of 6 | ENST00000370263.9 | NP_000735.1 | |
CHRNA4 | NM_001256573.2 | c.1101C>T | p.Ser367Ser | synonymous_variant | Exon 5 of 6 | NP_001243502.1 | ||
CHRNA4 | NR_046317.2 | n.1838C>T | non_coding_transcript_exon_variant | Exon 5 of 6 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.404 AC: 61427AN: 152032Hom.: 15016 Cov.: 34
GnomAD3 exomes AF: 0.471 AC: 116275AN: 247118Hom.: 29237 AF XY: 0.475 AC XY: 63808AN XY: 134266
GnomAD4 exome AF: 0.523 AC: 761794AN: 1456910Hom.: 205217 Cov.: 77 AF XY: 0.521 AC XY: 376959AN XY: 724028
GnomAD4 genome AF: 0.404 AC: 61447AN: 152150Hom.: 15024 Cov.: 34 AF XY: 0.408 AC XY: 30309AN XY: 74374
ClinVar
Submissions by phenotype
not specified Benign:4
- -
- -
This variant is classified as Benign based on local population frequency. This variant was detected in 74% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 69. Only high quality variants are reported. -
Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -
not provided Benign:3
- -
- -
This variant is associated with the following publications: (PMID: 28877969) -
Autosomal dominant nocturnal frontal lobe epilepsy 1 Benign:1
- -
Autosomal dominant nocturnal frontal lobe epilepsy Benign:1
- -
Inborn genetic diseases Benign:1
This alteration is classified as 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. -
NICOTINE ADDICTION, PROTECTION AGAINST Benign:1
- -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at