3-178543398-C-T

Variant names:

• chr3-178543398-C-T
• rs9832697
• NM_181361.3:c.-68+6687C>T

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+6687C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.175 in 152,178 control chromosomes in the GnomAD database, including 2,470 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 0.18 (2470 hom., cov: 32)
• Consequence: KCNMB2 NM_181361.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.02
• Publications: 2 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=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.24 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+6687C>T		intron	N/A	NP_852006.1
	KCNMB2-AS1	NR_126560.1		n.575-6002G>A		intron	N/A
	KCNMB2-AS1	NR_126561.1		n.638-16773G>A		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNMB2	ENST00000452583.6	TSL:1 MANE Select	c.-68+6687C>T		intron	N/A	ENSP00000397483.1
	ENSG00000275163	ENST00000614557.1	TSL:2	c.-68+124023C>T		intron	N/A	ENSP00000483415.1
	KCNMB2-AS1	ENST00000437488.5	TSL:1	n.522-6002G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.175 AC: 26609 AN: 152060 Hom.: 2462 Cov.: 32

Gnomad AFR AF: 0.127

Gnomad AMI AF: 0.105

Gnomad AMR AF: 0.213

Gnomad ASJ AF: 0.223

Gnomad EAS AF: 0.0549

Gnomad SAS AF: 0.252

Gnomad FIN AF: 0.259

Gnomad MID AF: 0.245

Gnomad NFE AF: 0.184

Gnomad OTH AF: 0.197

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

GnomAD4 genome AF: 0.175 AC: 26646 AN: 152178 Hom.: 2470 Cov.: 32 AF XY: 0.181 AC XY: 13458 AN XY: 74386

African (AFR) AF: 0.127 AC: 5263 AN: 41528

American (AMR) AF: 0.214 AC: 3267 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.223 AC: 774 AN: 3472

East Asian (EAS) AF: 0.0547 AC: 283 AN: 5176

South Asian (SAS) AF: 0.252 AC: 1215 AN: 4820

European-Finnish (FIN) AF: 0.259 AC: 2743 AN: 10580

Middle Eastern (MID) AF: 0.247 AC: 72 AN: 292

European-Non Finnish (NFE) AF: 0.184 AC: 12516 AN: 68000

Other (OTH) AF: 0.197 AC: 417 AN: 2116

Alfa AF: 0.174 Hom.: 1287

Bravo AF: 0.169

Asia WGS AF: 0.143 AC: 496 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	7.8
DANN	Benign	0.47
PhyloP100		1.0
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: rs9832697; hg19: chr3-178261186;