chr5-45695870-T-TCGC
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 1P and 9B. PM4_SupportingBP6BS1BS2
The NM_021072.4(HCN1):c.223_224insGCG(p.Gly74dup) variant causes a inframe insertion change. The variant allele was found at a frequency of 0.000223 in 1,563,444 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.00024 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00022 ( 0 hom. )
Consequence
HCN1
NM_021072.4 inframe_insertion
NM_021072.4 inframe_insertion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 6.52
Genes affected
HCN1 (HGNC:4845): (hyperpolarization activated cyclic nucleotide gated potassium channel 1) The membrane protein encoded by this gene is a hyperpolarization-activated cation channel that contributes to the native pacemaker currents in heart and neurons. The encoded protein can homodimerize or heterodimerize with other pore-forming subunits to form a potassium channel. This channel may act as a receptor for sour tastes. [provided by RefSeq, Oct 2011]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -8 ACMG points.
PM4
?
Nonframeshift variant in NON repetitive region in NM_021072.4. Strenght limited to Supporting due to length of the change: 1aa.
BP6
?
Variant 5-45695870-T-TCGC is Benign according to our data. Variant chr5-45695870-T-TCGC is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 412769.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Likely_benign=4}.
BS1
?
Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000236 (35/148110) while in subpopulation EAS AF= 0.00144 (7/4858). AF 95% confidence interval is 0.000676. There are 0 homozygotes in gnomad4. There are 19 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High AC in GnomAd at 35 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HCN1 | NM_021072.4 | c.223_224insGCG | p.Gly74dup | inframe_insertion | 1/8 | ENST00000303230.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HCN1 | ENST00000303230.6 | c.223_224insGCG | p.Gly74dup | inframe_insertion | 1/8 | 1 | NM_021072.4 | P2 | |
HCN1 | ENST00000634658.1 | c.223_224insGCG | p.Gly74dup | inframe_insertion | 1/2 | 3 | |||
HCN1 | ENST00000673735.1 | c.223_224insGCG | p.Gly74dup | inframe_insertion | 1/9 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.000236 AC: 35AN: 147992Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000152 AC: 25AN: 164440Hom.: 0 AF XY: 0.000215 AC XY: 20AN XY: 93110
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GnomAD4 exome AF: 0.000221 AC: 313AN: 1415334Hom.: 0 Cov.: 33 AF XY: 0.000228 AC XY: 160AN XY: 702528
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:4
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Oct 05, 2021 | - - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | May 24, 2016 | - - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 24, 2017 | 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
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 11, 2024 | - - |
HCN1-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Apr 22, 2022 | 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
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Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at