rs36004050
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Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1
The NM_139318.5(KCNH5):c.2088G>A(p.Val696Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0365 in 1,613,142 control chromosomes in the GnomAD database, including 1,359 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.031 ( 118 hom., cov: 32)
Exomes 𝑓: 0.037 ( 1241 hom. )
Consequence
KCNH5
NM_139318.5 synonymous
NM_139318.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.192
Genes affected
KCNH5 (HGNC:6254): (potassium voltage-gated channel subfamily H member 5) This gene encodes a member of voltage-gated potassium channels. Members of this family have diverse functions, including regulating neurotransmitter and hormone release, cardiac function, and cell volume. This protein is an outward-rectifying, noninactivating channel. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -19 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.46).
BP6
Variant 14-62708387-C-T is Benign according to our data. Variant chr14-62708387-C-T is described in ClinVar as [Benign]. Clinvar id is 416125.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=0.192 with no splicing effect.
BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0619 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
KCNH5 | NM_139318.5 | c.2088G>A | p.Val696Val | synonymous_variant | 11/11 | ENST00000322893.12 | NP_647479.2 | |
KCNH5 | NM_172375.3 | c.*55G>A | 3_prime_UTR_variant | 10/10 | NP_758963.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
KCNH5 | ENST00000322893.12 | c.2088G>A | p.Val696Val | synonymous_variant | 11/11 | 1 | NM_139318.5 | ENSP00000321427.7 | ||
KCNH5 | ENST00000420622 | c.*55G>A | 3_prime_UTR_variant | 10/10 | 1 | ENSP00000395439.2 |
Frequencies
GnomAD3 genomes AF: 0.0306 AC: 4650AN: 152100Hom.: 118 Cov.: 32
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GnomAD3 exomes AF: 0.0347 AC: 8697AN: 250560Hom.: 249 AF XY: 0.0361 AC XY: 4885AN XY: 135488
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GnomAD4 exome AF: 0.0371 AC: 54211AN: 1460924Hom.: 1241 Cov.: 34 AF XY: 0.0378 AC XY: 27460AN XY: 726772
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GnomAD4 genome AF: 0.0306 AC: 4655AN: 152218Hom.: 118 Cov.: 32 AF XY: 0.0325 AC XY: 2416AN XY: 74440
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ClinVar
Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Early infantile epileptic encephalopathy with suppression bursts Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Feb 01, 2024 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
KCNH5-related disorder Benign:1
Benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Mar 21, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at