rs919650074
Positions:
Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2
The NM_012282.4(KCNE5):c.123C>T(p.Val41=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000331 in 1,208,938 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 14 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.000044 ( 0 hom., 1 hem., cov: 24)
Exomes 𝑓: 0.000032 ( 0 hom. 13 hem. )
Consequence
KCNE5
NM_012282.4 synonymous
NM_012282.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.0100
Genes affected
KCNE5 (HGNC:6241): (potassium voltage-gated channel subfamily E regulatory subunit 5) This gene encodes a member of a family of single pass transmembrane domain proteins that function as ancillary subunits to voltage-gated potassium channels. Members of this family affect diverse processes in potassium channel regulation, including ion selectivity, voltage dependence, and anterograde recycling from the plasma membrane. Variants of this gene are associated with idiopathic ventricular fibrillation and Brugada syndrome. [provided by RefSeq, Nov 2016]
ACSL4 (HGNC:3571): (acyl-CoA synthetase long chain family member 4) The protein encoded by this gene is an isozyme of the long-chain fatty-acid-coenzyme A ligase family. Although differing in substrate specificity, subcellular localization, and tissue distribution, all isozymes of this family convert free long-chain fatty acids into fatty acyl-CoA esters, and thereby play a key role in lipid biosynthesis and fatty acid degradation. This isozyme preferentially utilizes arachidonate as substrate. The absence of this enzyme may contribute to the cognitive disability or Alport syndrome. Alternative splicing of this gene generates multiple transcript variants. [provided by RefSeq, Jan 2016]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -17 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.58).
BP6
?
Variant X-109624898-G-A is Benign according to our data. Variant chrX-109624898-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 532132.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-0.01 with no splicing effect.
BS2
?
High Hemizygotes in GnomAdExome4 at 13 gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KCNE5 | NM_012282.4 | c.123C>T | p.Val41= | synonymous_variant | 1/1 | ENST00000372101.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KCNE5 | ENST00000372101.3 | c.123C>T | p.Val41= | synonymous_variant | 1/1 | NM_012282.4 | P1 | ||
ACSL4 | ENST00000439581.1 | n.387-577C>T | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000442 AC: 5AN: 113076Hom.: 0 Cov.: 24 AF XY: 0.0000284 AC XY: 1AN XY: 35228
GnomAD3 genomes
?
AF:
AC:
5
AN:
113076
Hom.:
Cov.:
24
AF XY:
AC XY:
1
AN XY:
35228
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.0000284 AC: 5AN: 176132Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 64090
GnomAD3 exomes
AF:
AC:
5
AN:
176132
Hom.:
AF XY:
AC XY:
0
AN XY:
64090
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0000319 AC: 35AN: 1095862Hom.: 0 Cov.: 31 AF XY: 0.0000359 AC XY: 13AN XY: 362342
GnomAD4 exome
AF:
AC:
35
AN:
1095862
Hom.:
Cov.:
31
AF XY:
AC XY:
13
AN XY:
362342
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.0000442 AC: 5AN: 113076Hom.: 0 Cov.: 24 AF XY: 0.0000284 AC XY: 1AN XY: 35228
GnomAD4 genome
?
AF:
AC:
5
AN:
113076
Hom.:
Cov.:
24
AF XY:
AC XY:
1
AN XY:
35228
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 30, 2023 | 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. - |
Brugada syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jun 19, 2023 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at