rs13100616

Variant names:

• chr3-178681763-A-G
• rs13100616
• NM_181361.3:c.-67-125580A>G

Variant summary

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

The NM_181361.3(KCNMB2):​c.-67-125580A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.326 in 152,042 control chromosomes in the GnomAD database, including 8,809 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 0.33 (8809 hom., cov: 32)
• Consequence: KCNMB2 NM_181361.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.423
• 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.461 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNMB2	NM_181361.3	c.-67-125580A>G		intron_variant	Intron 1 of 4	ENST00000452583.6	NP_852006.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNMB2	ENST00000452583.6	c.-67-125580A>G		intron_variant	Intron 1 of 4	1	NM_181361.3	ENSP00000397483.1
ENSG00000275163	ENST00000614557.1	c.-67-125580A>G		intron_variant	Intron 1 of 4	2		ENSP00000483415.1

Frequencies

GnomAD3 genomes AF: 0.326 AC: 49597 AN: 151924 Hom.: 8802 Cov.: 32

Gnomad AFR AF: 0.467

Gnomad AMI AF: 0.270

Gnomad AMR AF: 0.251

Gnomad ASJ AF: 0.219

Gnomad EAS AF: 0.123

Gnomad SAS AF: 0.217

Gnomad FIN AF: 0.224

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.304

Gnomad OTH AF: 0.309

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

GnomAD4 genome AF: 0.326 AC: 49641 AN: 152042 Hom.: 8809 Cov.: 32 AF XY: 0.318 AC XY: 23648 AN XY: 74328

African (AFR) AF: 0.467 AC: 19358 AN: 41456

American (AMR) AF: 0.250 AC: 3820 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.219 AC: 761 AN: 3468

East Asian (EAS) AF: 0.123 AC: 634 AN: 5174

South Asian (SAS) AF: 0.217 AC: 1047 AN: 4818

European-Finnish (FIN) AF: 0.224 AC: 2374 AN: 10580

Middle Eastern (MID) AF: 0.289 AC: 85 AN: 294

European-Non Finnish (NFE) AF: 0.304 AC: 20663 AN: 67952

Other (OTH) AF: 0.309 AC: 653 AN: 2114

Alfa AF: 0.305 Hom.: 11343

Bravo AF: 0.334

Asia WGS AF: 0.186 AC: 646 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	6.8
DANN	Benign	0.71
PhyloP100		0.42
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: rs13100616; hg19: chr3-178399551;