NM_181361.3:c.-68+37854T>C

Variant names:

• chr3-178574565-T-C
• rs9290656
• NM_181361.3:c.-68+37854T>C

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+37854T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.254 in 152,052 control chromosomes in the GnomAD database, including 5,348 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 0.25 (5348 hom., cov: 32)
• Consequence: KCNMB2 NM_181361.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.15
• Publications: 4 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.391 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+37854T>C		intron	N/A	NP_852006.1
	KCNMB2	NM_001278911.2		c.-68+15581T>C		intron	N/A	NP_001265840.1
	KCNMB2	NM_005832.5		c.-145+15581T>C		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+37854T>C		intron	N/A	ENSP00000397483.1
	KCNMB2	ENST00000432997.5	TSL:1	c.-68+15581T>C		intron	N/A	ENSP00000407592.1
	ENSG00000275163	ENST00000614557.1	TSL:2	c.-68+155190T>C		intron	N/A	ENSP00000483415.1

Frequencies

GnomAD3 genomes AF: 0.254 AC: 38629 AN: 151936 Hom.: 5347 Cov.: 32

Gnomad AFR AF: 0.137

Gnomad AMI AF: 0.275

Gnomad AMR AF: 0.283

Gnomad ASJ AF: 0.346

Gnomad EAS AF: 0.405

Gnomad SAS AF: 0.320

Gnomad FIN AF: 0.373

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.280

Gnomad OTH AF: 0.263

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

GnomAD4 genome AF: 0.254 AC: 38637 AN: 152052 Hom.: 5348 Cov.: 32 AF XY: 0.261 AC XY: 19391 AN XY: 74292

African (AFR) AF: 0.137 AC: 5672 AN: 41514

American (AMR) AF: 0.283 AC: 4315 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.346 AC: 1201 AN: 3468

East Asian (EAS) AF: 0.405 AC: 2097 AN: 5172

South Asian (SAS) AF: 0.320 AC: 1540 AN: 4818

European-Finnish (FIN) AF: 0.373 AC: 3932 AN: 10540

Middle Eastern (MID) AF: 0.221 AC: 65 AN: 294

European-Non Finnish (NFE) AF: 0.280 AC: 18995 AN: 67956

Other (OTH) AF: 0.269 AC: 569 AN: 2112

Alfa AF: 0.272 Hom.: 24715

Bravo AF: 0.242

Asia WGS AF: 0.365 AC: 1273 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.94
DANN	Benign	0.59
PhyloP100		-1.2
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: rs9290656; hg19: chr3-178292353;