rs142280884
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 1P and 10B. PP2BP4_StrongBP6_ModerateBS2
The NM_021072.4(HCN1):c.2009C>T(p.Ala670Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000905 in 1,613,840 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A670T) has been classified as Uncertain significance.
Frequency
Consequence
NM_021072.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HCN1 | NM_021072.4 | c.2009C>T | p.Ala670Val | missense_variant | 8/8 | ENST00000303230.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HCN1 | ENST00000303230.6 | c.2009C>T | p.Ala670Val | missense_variant | 8/8 | 1 | NM_021072.4 | P2 | |
HCN1 | ENST00000673735.1 | c.*234C>T | 3_prime_UTR_variant | 9/9 | A2 | ||||
HCN1 | ENST00000637305.1 | n.1172C>T | non_coding_transcript_exon_variant | 7/7 | 5 |
Frequencies
GnomAD3 genomes AF: 0.0000855 AC: 13AN: 152070Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000438 AC: 11AN: 251360Hom.: 0 AF XY: 0.0000442 AC XY: 6AN XY: 135858
GnomAD4 exome AF: 0.0000910 AC: 133AN: 1461770Hom.: 0 Cov.: 32 AF XY: 0.0000894 AC XY: 65AN XY: 727192
GnomAD4 genome AF: 0.0000855 AC: 13AN: 152070Hom.: 0 Cov.: 32 AF XY: 0.0000942 AC XY: 7AN XY: 74290
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Uncertain significance, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Early infantile epileptic encephalopathy with suppression bursts Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Nov 27, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at