rs200033529
Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2
The NM_005477.3(HCN4):c.1560G>A(p.Leu520=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000397 in 1,613,976 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. L520L) has been classified as Benign.
Frequency
Consequence
NM_005477.3 synonymous
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Benign. Variant got -15 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HCN4 | NM_005477.3 | c.1560G>A | p.Leu520= | synonymous_variant | 4/8 | ENST00000261917.4 | |
HCN4 | XM_011521148.3 | c.342G>A | p.Leu114= | synonymous_variant | 3/7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HCN4 | ENST00000261917.4 | c.1560G>A | p.Leu520= | synonymous_variant | 4/8 | 1 | NM_005477.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152162Hom.: 0 Cov.: 34
GnomAD3 exomes AF: 0.0000398 AC: 10AN: 251440Hom.: 0 AF XY: 0.0000294 AC XY: 4AN XY: 135904
GnomAD4 exome AF: 0.0000424 AC: 62AN: 1461814Hom.: 0 Cov.: 32 AF XY: 0.0000454 AC XY: 33AN XY: 727226
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152162Hom.: 0 Cov.: 34 AF XY: 0.0000135 AC XY: 1AN XY: 74310
ClinVar
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 10, 2019 | - - |
Brugada syndrome 8 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 09, 2024 | - - |
Cardiovascular phenotype Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 01, 2019 | 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at