chr5-45695884-G-GCCGCCGCCA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 2P and 12B. PM4BP6_Very_StrongBS2

The NM_021072.4(HCN1):​c.201_209dupTGGCGGCGG​(p.Gly68_Gly70dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000163 in 1,529,784 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00018 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00016 ( 0 hom. )

Consequence

HCN1
NM_021072.4 disruptive_inframe_insertion

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 2.38
Variant links:
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 -10 ACMG points.

PM4
Nonframeshift variant in NON repetitive region in NM_021072.4.
BP6
Variant 5-45695884-G-GCCGCCGCCA is Benign according to our data. Variant chr5-45695884-G-GCCGCCGCCA is described in ClinVar as [Likely_benign]. Clinvar id is 412768.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS2
High AC in GnomAd4 at 27 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
HCN1NM_021072.4 linkc.201_209dupTGGCGGCGG p.Gly68_Gly70dup disruptive_inframe_insertion Exon 1 of 8 ENST00000303230.6 NP_066550.2 O60741Q86WJ6

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
HCN1ENST00000303230.6 linkc.201_209dupTGGCGGCGG p.Gly68_Gly70dup disruptive_inframe_insertion Exon 1 of 8 1 NM_021072.4 ENSP00000307342.4 O60741
HCN1ENST00000673735.1 linkc.201_209dupTGGCGGCGG p.Gly68_Gly70dup disruptive_inframe_insertion Exon 1 of 9 ENSP00000501107.1 A0A669KB45
HCN1ENST00000634658.1 linkc.201_209dupTGGCGGCGG p.Gly68_Gly70dup disruptive_inframe_insertion Exon 1 of 2 3 ENSP00000489134.1 A0A0U1RQR7

Frequencies

GnomAD3 genomes
AF:
0.000179
AC:
27
AN:
150518
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000195
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000132
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.0000968
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000237
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.000162
AC:
223
AN:
1379162
Hom.:
0
Cov.:
33
AF XY:
0.000167
AC XY:
114
AN XY:
681952
show subpopulations
Gnomad4 AFR exome
AF:
0.0000324
Gnomad4 AMR exome
AF:
0.0000298
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000276
Gnomad4 SAS exome
AF:
0.0000761
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000195
Gnomad4 OTH exome
AF:
0.0000699
GnomAD4 genome
AF:
0.000179
AC:
27
AN:
150622
Hom.:
0
Cov.:
32
AF XY:
0.000163
AC XY:
12
AN XY:
73604
show subpopulations
Gnomad4 AFR
AF:
0.000194
Gnomad4 AMR
AF:
0.000132
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.0000968
Gnomad4 NFE
AF:
0.000237
Gnomad4 OTH
AF:
0.00

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:1
Benign, no assertion criteria providedclinical testingGenome Diagnostics Laboratory, University Medical Center Utrecht-- -
Inborn genetic diseases Benign:1
Benign, criteria provided, single submitterclinical testingAmbry GeneticsJun 14, 2022This alteration is classified as 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 submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 30, 2025- -
not provided Benign:1
Likely benign, no assertion criteria providedclinical testingDiagnostic Laboratory, Department of Genetics, University Medical Center Groningen-- -
Intellectual disability Benign:1
Likely benign, no assertion criteria providedclinical testingCentre de Biologie Pathologie Génétique, Centre Hospitalier Universitaire de LilleJan 01, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs56064803; hg19: chr5-45695986; API