rs2656842
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_004137.4(KCNMB1):c.*78C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000285 in 1,438,790 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000030 ( 0 hom. )
Consequence
KCNMB1
NM_004137.4 3_prime_UTR
NM_004137.4 3_prime_UTR
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -1.25
Genes affected
KCNMB1 (HGNC:6285): (potassium calcium-activated channel subfamily M regulatory beta subunit 1) MaxiK channels are large conductance, voltage and calcium-sensitive potassium channels which are fundamental to the control of smooth muscle tone and neuronal excitability. MaxiK channels can be formed by 2 subunits: the pore-forming alpha subunit and the product of this gene, the modulatory beta subunit. Intracellular calcium regulates the physical association between the alpha and beta subunits. [provided by RefSeq, Jul 2008]
KCNIP1 (HGNC:15521): (potassium voltage-gated channel interacting protein 1) This gene encodes a member of the family of cytosolic voltage-gated potassium (Kv) channel-interacting proteins (KCNIPs), which belong to the neuronal calcium sensor (NCS) family of the calcium binding EF-hand proteins. They associate with Kv4 alpha subunits to form native Kv4 channel complexes. The encoded protein may regulate rapidly inactivating (A-type) currents, and hence neuronal membrane excitability, in response to changes in the concentration of intracellular calcium. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, May 2013]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.91).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KCNMB1 | NM_004137.4 | c.*78C>T | 3_prime_UTR_variant | 4/4 | ENST00000274629.9 | ||
KCNIP1 | NM_001034838.3 | c.88+24662G>A | intron_variant | ||||
KCNIP1 | XM_017009407.2 | c.88+24662G>A | intron_variant | ||||
KCNIP1 | XM_017009408.2 | c.88+24662G>A | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KCNMB1 | ENST00000274629.9 | c.*78C>T | 3_prime_UTR_variant | 4/4 | 1 | NM_004137.4 | P1 | ||
KCNIP1 | ENST00000377360.8 | c.88+24662G>A | intron_variant | 1 | P4 | ||||
KCNIP1 | ENST00000517344.1 | c.88+24662G>A | intron_variant, NMD_transcript_variant | 3 | |||||
KCNIP1 | ENST00000518527.1 | n.478+24662G>A | intron_variant, non_coding_transcript_variant | 4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000198 AC: 3AN: 151844Hom.: 0 Cov.: 33
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GnomAD4 exome AF: 0.0000295 AC: 38AN: 1286828Hom.: 0 Cov.: 20 AF XY: 0.0000503 AC XY: 32AN XY: 636034
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GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 151962Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74298
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ClinVar
Not reported inComputational scores
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BayesDel_noAF
Benign
Cadd
Benign
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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