rs2054399

Positions:

• chr3-178623794-G-A
• chr3-178623794-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_181361.3(KCNMB2):​c.-68+87083G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.691 in 152,002 control chromosomes in the GnomAD database, including 36,867 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 0.69 (36867 hom., cov: 31)
• Consequence: KCNMB2 NM_181361.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.794

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]

KCNMB2-AS1 (HGNC:51409): (KCNMB2 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.828 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNMB2	NM_181361.3	c.-68+87083G>A		intron_variant		ENST00000452583.6
KCNMB2-AS1	NR_126560.1	n.575-86398C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNMB2	ENST00000452583.6	c.-68+87083G>A		intron_variant		1	NM_181361.3	P1
KCNMB2-AS1	ENST00000437488.5	n.522-86398C>T		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.691 AC: 104915 AN: 151884 Hom.: 36830 Cov.: 31

Gnomad AFR AF: 0.836

Gnomad AMI AF: 0.627

Gnomad AMR AF: 0.686

Gnomad ASJ AF: 0.612

Gnomad EAS AF: 0.549

Gnomad SAS AF: 0.698

Gnomad FIN AF: 0.585

Gnomad MID AF: 0.672

Gnomad NFE AF: 0.635

Gnomad OTH AF: 0.689

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

GnomAD4 genome AF: 0.691 AC: 105005 AN: 152002 Hom.: 36867 Cov.: 31 AF XY: 0.687 AC XY: 51046 AN XY: 74266

Gnomad4 AFR AF: 0.836

Gnomad4 AMR AF: 0.687

Gnomad4 ASJ AF: 0.612

Gnomad4 EAS AF: 0.549

Gnomad4 SAS AF: 0.698

Gnomad4 FIN AF: 0.585

Gnomad4 NFE AF: 0.635

Gnomad4 OTH AF: 0.684

Alfa AF: 0.640 Hom.: 56662

Bravo AF: 0.700

Asia WGS AF: 0.606 AC: 2102 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.77
DANN	Benign	0.71

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

Publications

LitVar

Other links and lift over

dbSNP: rs2054399; hg19: chr3-178341582;