rs370113959
Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 1P and 18B. PP2BP4_ModerateBP6_Very_StrongBS1BS2
The NM_021072.4(HCN1):c.259C>T(p.Pro87Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000381 in 1,601,824 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. P87P) has been classified as Likely benign.
Frequency
Consequence
NM_021072.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -17 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HCN1 | NM_021072.4 | c.259C>T | p.Pro87Ser | missense_variant | 1/8 | ENST00000303230.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HCN1 | ENST00000303230.6 | c.259C>T | p.Pro87Ser | missense_variant | 1/8 | 1 | NM_021072.4 | P2 | |
HCN1 | ENST00000673735.1 | c.259C>T | p.Pro87Ser | missense_variant | 1/9 | A2 | |||
HCN1 | ENST00000634658.1 | c.259C>T | p.Pro87Ser | missense_variant | 1/2 | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.000205 AC: 31AN: 151400Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000431 AC: 10AN: 232052Hom.: 0 AF XY: 0.0000468 AC XY: 6AN XY: 128270
GnomAD4 exome AF: 0.0000207 AC: 30AN: 1450320Hom.: 0 Cov.: 33 AF XY: 0.0000208 AC XY: 15AN XY: 721874
GnomAD4 genome ? AF: 0.000205 AC: 31AN: 151504Hom.: 0 Cov.: 32 AF XY: 0.000176 AC XY: 13AN XY: 74032
ClinVar
Submissions by phenotype
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 13, 2016 | This alteration is classified as likely 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. - |
Early infantile epileptic encephalopathy with suppression bursts Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 16, 2024 | - - |
HCN1-related condition Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | May 21, 2023 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at