rs748849525
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Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 2P and 16B. PM4BP6_Very_StrongBS1BS2
The NM_021072.4(HCN1):βc.200_223delβ(p.Gly67_Gly74del) variant causes a inframe deletion change. The variant allele was found at a frequency of 0.0000256 in 1,563,470 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Likely benign (β β ).
Frequency
Genomes: π 0.000014 ( 0 hom., cov: 32)
Exomes π: 0.000027 ( 1 hom. )
Consequence
HCN1
NM_021072.4 inframe_deletion
NM_021072.4 inframe_deletion
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 -14 ACMG points.
PM4
Nonframeshift variant in NON repetitive region in NM_021072.4.
BP6
Variant 5-45695870-TCGCCGCCGCCGCCGCCGCCGCCAC-T is Benign according to our data. Variant chr5-45695870-TCGCCGCCGCCGCCGCCGCCGCCAC-T is described in ClinVar as [Likely_benign]. Clinvar id is 461368.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.0000268 (38/1415358) while in subpopulation AMR AF= 0.000943 (37/39240). AF 95% confidence interval is 0.000702. There are 1 homozygotes in gnomad4_exome. There are 18 alleles in male gnomad4_exome subpopulation. This position pass quality control queck.
BS2
High AC in GnomAdExome4 at 38 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
HCN1 | NM_021072.4 | c.200_223del | p.Gly67_Gly74del | inframe_deletion | 1/8 | ENST00000303230.6 | NP_066550.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
HCN1 | ENST00000303230.6 | c.200_223del | p.Gly67_Gly74del | inframe_deletion | 1/8 | 1 | NM_021072.4 | ENSP00000307342 | P2 | |
HCN1 | ENST00000634658.1 | c.200_223del | p.Gly67_Gly74del | inframe_deletion | 1/2 | 3 | ENSP00000489134 | |||
HCN1 | ENST00000673735.1 | c.200_223del | p.Gly67_Gly74del | inframe_deletion | 1/9 | ENSP00000501107 | A2 |
Frequencies
GnomAD3 genomes AF: 0.0000135 AC: 2AN: 147994Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000195 AC: 32AN: 164440Hom.: 2 AF XY: 0.000150 AC XY: 14AN XY: 93110
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GnomAD4 exome AF: 0.0000268 AC: 38AN: 1415358Hom.: 1 AF XY: 0.0000256 AC XY: 18AN XY: 702546
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GnomAD4 genome AF: 0.0000135 AC: 2AN: 148112Hom.: 0 Cov.: 32 AF XY: 0.0000138 AC XY: 1AN XY: 72348
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 17, 2016 | 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 | Labcorp Genetics (formerly Invitae), Labcorp | Dec 01, 2023 | - - |
Computational scores
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Find out detailed SpliceAI scores and Pangolin per-transcript scores at