rs2218248

Positions:

• chr3-178391430-G-A

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNMB2	ENST00000437510.5	c.-68+118424G>A		intron_variant		4		ENSP00000395807

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

Gnomad4 AFR AF: 0.321

Gnomad4 AMR AF: 0.414

Gnomad4 ASJ AF: 0.295

Gnomad4 EAS AF: 0.578

Gnomad4 SAS AF: 0.367

Gnomad4 FIN AF: 0.396

Gnomad4 NFE AF: 0.353

Gnomad4 OTH AF: 0.388

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 v4.3

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2218248; hg19: chr3-178109218;