rs2218248

Variant names:

• chr3-178391430-G-A
• rs2218248
• ENST00000437510.5:c.-68+118424G>A

Variant summary

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

The ENST00000437510.5(KCNMB2):​c.-68+118424G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.36 in 151,648 control chromosomes in the GnomAD database, including 9,938 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 0.36 (9938 hom., cov: 32)
• Consequence: KCNMB2 ENST00000437510.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.67
• Publications: 0 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.56 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000437510.5. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNMB2	ENST00000437510.5	TSL:4	c.-68+118424G>A		intron	N/A	ENSP00000395807.1

Frequencies

GnomAD3 genomes AF: 0.360 AC: 54508 AN: 151530 Hom.: 9928 Cov.: 32

Gnomad AFR AF: 0.321

Gnomad AMI AF: 0.252

Gnomad AMR AF: 0.414

Gnomad ASJ AF: 0.295

Gnomad EAS AF: 0.578

Gnomad SAS AF: 0.367

Gnomad FIN AF: 0.396

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.353

Gnomad OTH AF: 0.386

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

GnomAD4 genome AF: 0.360 AC: 54547 AN: 151648 Hom.: 9938 Cov.: 32 AF XY: 0.363 AC XY: 26910 AN XY: 74102

African (AFR) AF: 0.321 AC: 13284 AN: 41408

American (AMR) AF: 0.414 AC: 6300 AN: 15210

Ashkenazi Jewish (ASJ) AF: 0.295 AC: 1019 AN: 3460

East Asian (EAS) AF: 0.578 AC: 2980 AN: 5158

South Asian (SAS) AF: 0.367 AC: 1766 AN: 4812

European-Finnish (FIN) AF: 0.396 AC: 4170 AN: 10538

Middle Eastern (MID) AF: 0.303 AC: 89 AN: 294

European-Non Finnish (NFE) AF: 0.353 AC: 23891 AN: 67748

Other (OTH) AF: 0.388 AC: 818 AN: 2108

Alfa AF: 0.362 Hom.: 1695

Bravo AF: 0.365

Asia WGS AF: 0.466 AC: 1613 AN: 3460

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.20
DANN	Benign	0.35
PhyloP100		-1.7

Splicing

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

Other links and lift over

dbSNP: rs2218248; hg19: chr3-178109218;