chr5-45695870-T-TCGCCGC
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM4BS2
The NM_021072.4(HCN1):c.218_223dupGCGGCG(p.Gly73_Gly74dup) variant causes a conservative inframe insertion change. The variant allele was found at a frequency of 0.000108 in 1,563,460 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_021072.4 conservative_inframe_insertion
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
HCN1 | ENST00000303230.6 | c.218_223dupGCGGCG | p.Gly73_Gly74dup | conservative_inframe_insertion | Exon 1 of 8 | 1 | NM_021072.4 | ENSP00000307342.4 | ||
HCN1 | ENST00000673735.1 | c.218_223dupGCGGCG | p.Gly73_Gly74dup | conservative_inframe_insertion | Exon 1 of 9 | ENSP00000501107.1 | ||||
HCN1 | ENST00000634658.1 | c.218_223dupGCGGCG | p.Gly73_Gly74dup | conservative_inframe_insertion | Exon 1 of 2 | 3 | ENSP00000489134.1 |
Frequencies
GnomAD3 genomes AF: 0.000122 AC: 18AN: 147994Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.000107 AC: 151AN: 1415348Hom.: 0 Cov.: 33 AF XY: 0.000108 AC XY: 76AN XY: 702536
GnomAD4 genome AF: 0.000122 AC: 18AN: 148112Hom.: 0 Cov.: 32 AF XY: 0.000124 AC XY: 9AN XY: 72348
ClinVar
Submissions by phenotype
not provided Uncertain:2
In-frame duplication of 2 amino acids in a non-repeat region; Has not been previously published as pathogenic or benign to our knowledge -
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Early infantile epileptic encephalopathy with suppression bursts Uncertain:1
This variant, c.218_223dup, results in the insertion of 2 amino acid(s) of the HCN1 protein (p.Gly73_Gly74dup), but otherwise preserves the integrity of the reading frame. 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 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 (internal data). ClinVar contains an entry for this variant (Variation ID: 647637). 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