chr3-178574565-T-C

Position:

• chr3-178574565-T-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+37854T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.254 in 152,052 control chromosomes in the GnomAD database, including 5,348 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 0.25 (5348 hom., cov: 32)
• Consequence: KCNMB2 NM_181361.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.15

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:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.391 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNMB2	NM_181361.3	c.-68+37854T>C		intron_variant		ENST00000452583.6	NP_852006.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNMB2	ENST00000452583.6	c.-68+37854T>C		intron_variant		1	NM_181361.3	ENSP00000397483.1
ENSG00000275163	ENST00000614557.1	c.-68+155190T>C		intron_variant		2		ENSP00000483415.1

Frequencies

GnomAD3 genomes AF: 0.254 AC: 38629 AN: 151936 Hom.: 5347 Cov.: 32

Gnomad AFR AF: 0.137

Gnomad AMI AF: 0.275

Gnomad AMR AF: 0.283

Gnomad ASJ AF: 0.346

Gnomad EAS AF: 0.405

Gnomad SAS AF: 0.320

Gnomad FIN AF: 0.373

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.280

Gnomad OTH AF: 0.263

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

GnomAD4 genome AF: 0.254 AC: 38637 AN: 152052 Hom.: 5348 Cov.: 32 AF XY: 0.261 AC XY: 19391 AN XY: 74292

Gnomad4 AFR AF: 0.137

Gnomad4 AMR AF: 0.283

Gnomad4 ASJ AF: 0.346

Gnomad4 EAS AF: 0.405

Gnomad4 SAS AF: 0.320

Gnomad4 FIN AF: 0.373

Gnomad4 NFE AF: 0.280

Gnomad4 OTH AF: 0.269

Alfa AF: 0.277 Hom.: 12417

Bravo AF: 0.242

Asia WGS AF: 0.365 AC: 1273 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.94
DANN	Benign	0.59

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: rs9290656; hg19: chr3-178292353;