rs867816182
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Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2
The NM_005477.3(HCN4):c.3354C>T(p.Leu1118=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000135 in 1,410,448 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.000013 ( 0 hom. )
Consequence
HCN4
NM_005477.3 synonymous
NM_005477.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.334
Genes affected
HCN4 (HGNC:16882): (hyperpolarization activated cyclic nucleotide gated potassium channel 4) This gene encodes a member of the hyperpolarization-activated cyclic nucleotide-gated potassium channels. The encoded protein shows slow kinetics of activation and inactivation, and is necessary for the cardiac pacemaking process. This channel may also mediate responses to sour stimuli. Mutations in this gene have been linked to sick sinus syndrome 2, also known as atrial fibrillation with bradyarrhythmia or familial sinus bradycardia. Two pseudogenes have been identified on chromosome 15. [provided by RefSeq, Oct 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -11 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.9).
BP6
?
Variant 15-73322739-G-A is Benign according to our data. Variant chr15-73322739-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 470666.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=0.334 with no splicing effect.
BS2
?
High AC in GnomAdExome4 at 19 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HCN4 | NM_005477.3 | c.3354C>T | p.Leu1118= | synonymous_variant | 8/8 | ENST00000261917.4 | |
HCN4 | XM_011521148.3 | c.2136C>T | p.Leu712= | synonymous_variant | 7/7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HCN4 | ENST00000261917.4 | c.3354C>T | p.Leu1118= | synonymous_variant | 8/8 | 1 | NM_005477.3 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
GnomAD3 exomes AF: 0.0000189 AC: 3AN: 158494Hom.: 0 AF XY: 0.0000234 AC XY: 2AN XY: 85530
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GnomAD4 exome AF: 0.0000135 AC: 19AN: 1410448Hom.: 0 Cov.: 36 AF XY: 0.0000215 AC XY: 15AN XY: 696750
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GnomAD4 genome ? Cov.: 33
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Brugada syndrome 8 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | May 04, 2020 | - - |
Computational scores
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Name
Calibrated prediction
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at