NM_181361.3:c.-68+87083G>A

Variant names:

• chr3-178623794-G-A
• rs2054399
• NM_181361.3:c.-68+87083G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_181361.3(KCNMB2):​c.-68+87083G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.691 in 152,002 control chromosomes in the GnomAD database, including 36,867 homozygotes. 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 0.69 (36867 hom., cov: 31)
• Consequence: KCNMB2 NM_181361.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.794
• Publications: 11 publications found

Genes affected

KCNMB2 (HGNC:6286): (potassium calcium-activated channel subfamily M regulatory beta subunit 2) 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 modulatory beta subunit. The protein encoded by this gene is an auxiliary beta subunit which decreases the activation time of MaxiK alpha subunit currents. Alternative splicing results in multiple transcript variants of this gene. Additional variants are discussed in the literature, but their full length nature has not been described. [provided by RefSeq, Jul 2013]

ENSG00000275163 (HGNC:):

KCNMB2-AS1 (HGNC:51409): (KCNMB2 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.828 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_181361.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNMB2	NM_181361.3	MANE Select	c.-68+87083G>A		intron	N/A	NP_852006.1
	KCNMB2	NM_001278911.2		c.-68+64810G>A		intron	N/A	NP_001265840.1
	KCNMB2	NM_005832.5		c.-145+64810G>A		intron	N/A	NP_005823.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNMB2	ENST00000452583.6	TSL:1 MANE Select	c.-68+87083G>A		intron	N/A	ENSP00000397483.1
	KCNMB2	ENST00000432997.5	TSL:1	c.-68+64810G>A		intron	N/A	ENSP00000407592.1
	ENSG00000275163	ENST00000614557.1	TSL:2	c.-67-183549G>A		intron	N/A	ENSP00000483415.1

Frequencies

GnomAD3 genomes AF: 0.691 AC: 104915 AN: 151884 Hom.: 36830 Cov.: 31

Gnomad AFR AF: 0.836

Gnomad AMI AF: 0.627

Gnomad AMR AF: 0.686

Gnomad ASJ AF: 0.612

Gnomad EAS AF: 0.549

Gnomad SAS AF: 0.698

Gnomad FIN AF: 0.585

Gnomad MID AF: 0.672

Gnomad NFE AF: 0.635

Gnomad OTH AF: 0.689

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.691 AC: 105005 AN: 152002 Hom.: 36867 Cov.: 31 AF XY: 0.687 AC XY: 51046 AN XY: 74266

African (AFR) AF: 0.836 AC: 34673 AN: 41482

American (AMR) AF: 0.687 AC: 10483 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.612 AC: 2126 AN: 3472

East Asian (EAS) AF: 0.549 AC: 2827 AN: 5152

South Asian (SAS) AF: 0.698 AC: 3352 AN: 4804

European-Finnish (FIN) AF: 0.585 AC: 6157 AN: 10532

Middle Eastern (MID) AF: 0.664 AC: 194 AN: 292

European-Non Finnish (NFE) AF: 0.635 AC: 43178 AN: 67976

Other (OTH) AF: 0.684 AC: 1444 AN: 2112

Alfa AF: 0.655 Hom.: 99940

Bravo AF: 0.700

Asia WGS AF: 0.606 AC: 2102 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.77
DANN	Benign	0.71
PhyloP100		-0.79
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2054399; hg19: chr3-178341582;