5-45695870-TCGCCGCCGCCGCCGCCGCCGC-TCGCCGCCGCCGCCGCCGCCGCCGCCGC
Variant summary
Our verdict is Likely benign. The variant received -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
Genomes: 𝑓 0.00012 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00011 ( 0 hom. )
Consequence
HCN1
NM_021072.4 conservative_inframe_insertion
NM_021072.4 conservative_inframe_insertion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 6.52
Publications
1 publications found
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]
HCN1 Gene-Disease associations (from GenCC):
- developmental and epileptic encephalopathy, 24Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
- generalized epilepsy with febrile seizures plusInheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
- generalized epilepsy with febrile seizures plus, type 10Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
- undetermined early-onset epileptic encephalopathyInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Likely_benign. The variant received -2 ACMG points.
PM4
Nonframeshift variant in NON repetitive region in NM_021072.4.
BS2
High AC in GnomAd4 at 18 AD gene.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_021072.4. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| HCN1 | NM_021072.4 | MANE Select | c.218_223dupGCGGCG | p.Gly73_Gly74dup | conservative_inframe_insertion | Exon 1 of 8 | NP_066550.2 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| HCN1 | ENST00000303230.6 | TSL:1 MANE Select | c.218_223dupGCGGCG | p.Gly73_Gly74dup | conservative_inframe_insertion | Exon 1 of 8 | ENSP00000307342.4 | ||
| HCN1 | ENST00000947598.1 | c.218_223dupGCGGCG | p.Gly73_Gly74dup | conservative_inframe_insertion | Exon 1 of 8 | ENSP00000617657.1 | |||
| HCN1 | ENST00000673735.1 | c.218_223dupGCGGCG | p.Gly73_Gly74dup | conservative_inframe_insertion | Exon 1 of 9 | ENSP00000501107.1 |
Frequencies
GnomAD3 genomes 0.000122 AC: 18AN: 147994Hom.: 0 Cov.: 32 show subpopulations
GnomAD3 genomes
AF:
AC:
18
AN:
147994
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome AF: 0.000107 AC: 151AN: 1415348Hom.: 0 Cov.: 33 AF XY: 0.000108 AC XY: 76AN XY: 702536 show subpopulations
GnomAD4 exome
AF:
AC:
151
AN:
1415348
Hom.:
Cov.:
33
AF XY:
AC XY:
76
AN XY:
702536
show subpopulations
African (AFR)
AF:
AC:
2
AN:
31432
American (AMR)
AF:
AC:
3
AN:
39238
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
24940
East Asian (EAS)
AF:
AC:
7
AN:
37864
South Asian (SAS)
AF:
AC:
16
AN:
81868
European-Finnish (FIN)
AF:
AC:
0
AN:
41108
Middle Eastern (MID)
AF:
AC:
1
AN:
5298
European-Non Finnish (NFE)
AF:
AC:
108
AN:
1095100
Other (OTH)
AF:
AC:
14
AN:
58500
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.446
Heterozygous variant carriers
0
8
16
24
32
40
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
0
10
20
30
40
50
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome 0.000122 AC: 18AN: 148112Hom.: 0 Cov.: 32 AF XY: 0.000124 AC XY: 9AN XY: 72348 show subpopulations
GnomAD4 genome
AF:
AC:
18
AN:
148112
Hom.:
Cov.:
32
AF XY:
AC XY:
9
AN XY:
72348
show subpopulations
African (AFR)
AF:
AC:
1
AN:
40302
American (AMR)
AF:
AC:
5
AN:
15028
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3420
East Asian (EAS)
AF:
AC:
1
AN:
4858
South Asian (SAS)
AF:
AC:
3
AN:
4618
European-Finnish (FIN)
AF:
AC:
0
AN:
10108
Middle Eastern (MID)
AF:
AC:
0
AN:
264
European-Non Finnish (NFE)
AF:
AC:
7
AN:
66570
Other (OTH)
AF:
AC:
1
AN:
2058
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.478
Heterozygous variant carriers
0
1
2
4
5
6
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Genome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
Hom.:
ClinVar
ClinVar submissions as Germline
View on ClinVar Significance:Uncertain significance
Revision:criteria provided, multiple submitters, no conflicts
Pathogenic
VUS
Benign
Condition
-
2
-
not provided (2)
-
1
-
Developmental and epileptic encephalopathy (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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