chr5-45695758-G-T
Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6BP7BS2
The NM_021072.4(HCN1):c.336C>A(p.Arg112Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000013 in 1,460,114 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_021072.4 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -10 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
HCN1 | ENST00000303230.6 | c.336C>A | p.Arg112Arg | synonymous_variant | Exon 1 of 8 | 1 | NM_021072.4 | ENSP00000307342.4 | ||
HCN1 | ENST00000673735.1 | c.336C>A | p.Arg112Arg | synonymous_variant | Exon 1 of 9 | ENSP00000501107.1 | ||||
HCN1 | ENST00000634658.1 | c.336C>A | p.Arg112Arg | synonymous_variant | Exon 1 of 2 | 3 | ENSP00000489134.1 | |||
HCN1 | ENST00000638054.1 | n.-33C>A | upstream_gene_variant | 5 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.00000403 AC: 1AN: 247950Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135154
GnomAD4 exome AF: 0.0000130 AC: 19AN: 1460114Hom.: 1 Cov.: 33 AF XY: 0.00000826 AC XY: 6AN XY: 726418
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:1
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HCN1: BP4, BP7 -
Inborn genetic diseases Benign:1
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
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at