chr15-73323537-C-T
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_005477.3(HCN4):c.2556G>A(p.Pro852=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0453 in 1,601,002 control chromosomes in the GnomAD database, including 1,989 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. P852P) has been classified as Likely benign.
Frequency
Consequence
NM_005477.3 synonymous
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Benign. Variant got -21 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HCN4 | NM_005477.3 | c.2556G>A | p.Pro852= | synonymous_variant | 8/8 | ENST00000261917.4 | |
HCN4 | XM_011521148.3 | c.1338G>A | p.Pro446= | synonymous_variant | 7/7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HCN4 | ENST00000261917.4 | c.2556G>A | p.Pro852= | synonymous_variant | 8/8 | 1 | NM_005477.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0371 AC: 5651AN: 152160Hom.: 148 Cov.: 33
GnomAD3 exomes AF: 0.0489 AC: 11512AN: 235532Hom.: 395 AF XY: 0.0476 AC XY: 6113AN XY: 128470
GnomAD4 exome AF: 0.0461 AC: 66785AN: 1448724Hom.: 1839 Cov.: 36 AF XY: 0.0460 AC XY: 33153AN XY: 721108
GnomAD4 genome AF: 0.0372 AC: 5661AN: 152278Hom.: 150 Cov.: 33 AF XY: 0.0366 AC XY: 2727AN XY: 74456
ClinVar
Submissions by phenotype
not specified Benign:7
Benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Apr 04, 2023 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 16, 2014 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jul 05, 2013 | - - |
Benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Sick sinus syndrome 2, autosomal dominant Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Brugada syndrome 8 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Cardiovascular phenotype Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 19, 2015 | This 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at