KCNMB1 p.Val81Leu

Variant names:

• chr5-170383744-C-A
• NM_004137.4:c.241G>T
• KCNMB1 p.Val81Leu

Your query was ambiguous. Multiple possible variants found:

• chr5-170383744-C-A
• chr5-170383744-C-G
• chr5-170383742-CAC-TAA
• chr5-170383742-CAC-AAG
• chr5-170383742-CAC-GAG
• chr5-170383742-CAC-TAG

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004137.4(KCNMB1):​c.241G>T​(p.Val81Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: KCNMB1 NM_004137.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.26
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18970081).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004137.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNMB1	NM_004137.4	MANE Select	c.241G>T	p.Val81Leu	missense	Exon 3 of 4	NP_004128.1	Q16558-1
	KCNIP1	NM_001034838.3		c.88+29780C>A		intron	N/A	NP_001030010.1	Q9NZI2-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNMB1	ENST00000274629.9	TSL:1 MANE Select	c.241G>T	p.Val81Leu	missense	Exon 3 of 4	ENSP00000274629.3	Q16558-1
	KCNIP1	ENST00000377360.8	TSL:1	c.88+29780C>A		intron	N/A	ENSP00000366577.4	Q9NZI2-4
	KCNMB1	ENST00000962422.1		c.241G>T	p.Val81Leu	missense	Exon 3 of 4	ENSP00000632481.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.50
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Benign	0.038	T
Eigen	Benign	0.18
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.83	L
PhyloP100		2.3
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	0.24	N
REVEL	Benign	0.23
Sift	Benign	1.0	T
Sift4G	Benign	0.67	T
Varity_R		0.089
gMVP		0.31
Mutation Taster		=74/26	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr5-169810748;