rs1060500094
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP2BP6_Moderate
The NM_021072.4(HCN1):āc.2561G>Cā(p.Arg854Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00000658 in 152,014 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (ā ). Synonymous variant affecting the same amino acid position (i.e. R854R) has been classified as Likely benign.
Frequency
Genomes: š 0.0000066 ( 0 hom., cov: 32)
Consequence
HCN1
NM_021072.4 missense
NM_021072.4 missense
Scores
4
7
8
Clinical Significance
Conservation
PhyloP100: 3.67
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 Uncertain_significance. Variant got 1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP2
Missense variant in gene, where missense usually causes diseases (based on misZ statistic), HCN1. . Gene score misZ 3.6647 (greater than the threshold 3.09). Trascript score misZ 3.2427 (greater than threshold 3.09). GenCC has associacion of gene with generalized epilepsy with febrile seizures plus, type 10, undetermined early-onset epileptic encephalopathy, developmental and epileptic encephalopathy, 24, generalized epilepsy with febrile seizures plus.
BP6
Variant 5-45262033-C-G is Benign according to our data. Variant chr5-45262033-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 404095.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HCN1 | NM_021072.4 | c.2561G>C | p.Arg854Pro | missense_variant | 8/8 | ENST00000303230.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HCN1 | ENST00000303230.6 | c.2561G>C | p.Arg854Pro | missense_variant | 8/8 | 1 | NM_021072.4 | P2 | |
HCN1 | ENST00000673735.1 | c.*786G>C | 3_prime_UTR_variant | 9/9 | A2 | ||||
HCN1 | ENST00000637305.1 | n.1724G>C | non_coding_transcript_exon_variant | 7/7 | 5 |
Frequencies
GnomAD3 genomes AF: 0.00000658 AC: 1AN: 152014Hom.: 0 Cov.: 32
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GnomAD4 exome Cov.: 32
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GnomAD4 genome AF: 0.00000658 AC: 1AN: 152014Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74218
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Early infantile epileptic encephalopathy with suppression bursts Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | May 20, 2023 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
T
M_CAP
Uncertain
D
MetaRNN
Uncertain
T
MetaSVM
Pathogenic
D
MutationAssessor
Benign
L
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Uncertain
Sift
Benign
T
Sift4G
Benign
T
Polyphen
D
Vest4
MutPred
Loss of methylation at R854 (P = 0.0238);
MVP
MPC
ClinPred
D
GERP RS
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gMVP
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