5-45695884-G-GCCGCCGCCACCGCCGCCA
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PM4
The NM_021072.4(HCN1):c.192_209dupTGGCGGCGGTGGCGGCGG(p.Gly65_Gly70dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000133 in 150,518 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_021072.4 disruptive_inframe_insertion
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
HCN1 | ENST00000303230.6 | c.192_209dupTGGCGGCGGTGGCGGCGG | p.Gly65_Gly70dup | disruptive_inframe_insertion | Exon 1 of 8 | 1 | NM_021072.4 | ENSP00000307342.4 | ||
HCN1 | ENST00000673735.1 | c.192_209dupTGGCGGCGGTGGCGGCGG | p.Gly65_Gly70dup | disruptive_inframe_insertion | Exon 1 of 9 | ENSP00000501107.1 | ||||
HCN1 | ENST00000634658.1 | c.192_209dupTGGCGGCGGTGGCGGCGG | p.Gly65_Gly70dup | disruptive_inframe_insertion | Exon 1 of 2 | 3 | ENSP00000489134.1 | |||
HCN1 | ENST00000638054.1 | n.-177_-160dupTGGCGGCGGTGGCGGCGG | upstream_gene_variant | 5 |
Frequencies
GnomAD3 genomes AF: 0.0000133 AC: 2AN: 150518Hom.: 0 Cov.: 32
GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000399 AC: 55AN: 1379168Hom.: 0 Cov.: 33 AF XY: 0.0000411 AC XY: 28AN XY: 681952
GnomAD4 genome AF: 0.0000133 AC: 2AN: 150518Hom.: 0 Cov.: 32 AF XY: 0.0000272 AC XY: 2AN XY: 73490
ClinVar
Submissions by phenotype
Early infantile epileptic encephalopathy with suppression bursts Uncertain:1
The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant, c.192_209dup, results in the insertion of 6 amino acid(s) of the HCN1 protein (p.Gly69_Gly74dup), but otherwise preserves the integrity of the reading frame. This variant has not been reported in the literature in individuals affected with HCN1-related conditions. This variant has been observed in at least one individual who was not affected with HCN1-related conditions (Invitae). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at