3-178712151-A-T

Variant names:

• chr3-178712151-A-T
• rs9290663
• NM_181361.3:c.-67-95192A>T

Variant summary

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

The NM_181361.3(KCNMB2):​c.-67-95192A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.207 in 152,150 control chromosomes in the GnomAD database, including 3,823 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 0.21 (3823 hom., cov: 32)
• Consequence: KCNMB2 NM_181361.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0130
• Publications: 15 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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.326 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNMB2	NM_181361.3	c.-67-95192A>T		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.-67-95192A>T		intron_variant	Intron 1 of 4	1	NM_181361.3	ENSP00000397483.1
ENSG00000275163	ENST00000614557.1	c.-67-95192A>T		intron_variant	Intron 1 of 4	2		ENSP00000483415.1

Frequencies

GnomAD3 genomes AF: 0.207 AC: 31398 AN: 152032 Hom.: 3799 Cov.: 32

Gnomad AFR AF: 0.330

Gnomad AMI AF: 0.0779

Gnomad AMR AF: 0.142

Gnomad ASJ AF: 0.248

Gnomad EAS AF: 0.236

Gnomad SAS AF: 0.234

Gnomad FIN AF: 0.174

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.145

Gnomad OTH AF: 0.222

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

GnomAD4 genome AF: 0.207 AC: 31453 AN: 152150 Hom.: 3823 Cov.: 32 AF XY: 0.208 AC XY: 15475 AN XY: 74380

African (AFR) AF: 0.331 AC: 13727 AN: 41482

American (AMR) AF: 0.142 AC: 2171 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.248 AC: 862 AN: 3470

East Asian (EAS) AF: 0.235 AC: 1217 AN: 5176

South Asian (SAS) AF: 0.233 AC: 1125 AN: 4824

European-Finnish (FIN) AF: 0.174 AC: 1840 AN: 10586

Middle Eastern (MID) AF: 0.299 AC: 88 AN: 294

European-Non Finnish (NFE) AF: 0.145 AC: 9891 AN: 68016

Other (OTH) AF: 0.218 AC: 461 AN: 2116

Alfa AF: 0.163 Hom.: 1201

Bravo AF: 0.210

Asia WGS AF: 0.270 AC: 939 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.3
DANN	Benign	0.72
PhyloP100		-0.013
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: rs9290663; hg19: chr3-178429939;