Genetic Variant KCNMB3:p.Val252TyrfsTer4 (chr3-179242978-CT-C) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_171830.2(KCNMB3):c.753delA(p.Val252TyrfsTer4) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0659 in 1,607,104 control chromosomes in the GnomAD database, including 4,862 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.10 ( 1183 hom., cov: 28)

Exomes 𝑓: 0.062 ( 3679 hom. )

Consequence

KCNMB3
NM_171830.2 frameshift

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.485

Variant links:

Genes affected

KCNMB3 (HGNC:6287): (potassium calcium-activated channel subfamily M regulatory beta subunit 3) 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 may partially inactivate or slightly decrease the activation time of MaxiK alpha subunit currents. Alternative splicing results in multiple transcript variants. A related pseudogene has been identified on chromosome 22. [provided by RefSeq, Jul 2009]

KCNMB3 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP6

Variant 3-179242978-CT-C is Benign according to our data. Variant chr3-179242978-CT-C is described in ClinVar as [Benign]. Clinvar id is 403000.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.207 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNMB3	NM_171830.2 link	c.753delA	p.Val252TyrfsTer4	frameshift_variant	Exon 3 of 3	ENST00000392685.7	NP_741981.1	Q9NPA1-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNMB3	ENST00000392685.7 link	c.753delA	p.Val252TyrfsTer4	frameshift_variant	Exon 3 of 3	1	NM_171830.2	ENSP00000376451.2		Q9NPA1-3

Frequencies

GnomAD3 genomes

AF:

0.100

AC:

15213

AN:

151834

Hom.:

1179

Cov.:

show subpopulations

Gnomad AFR

AF:

0.211

Gnomad AMI

AF:

0.0811

Gnomad AMR

AF:

0.0777

Gnomad ASJ

AF:

0.119

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.0148

Gnomad FIN

AF:

0.0170

Gnomad MID

AF:

0.172

Gnomad NFE

AF:

0.0632

Gnomad OTH

AF:

0.108

GnomAD3 exomes

AF:

0.0624

AC:

15188

AN:

243254

Hom.:

780

AF XY:

0.0595

AC XY:

7810

AN XY:

131338

show subpopulations

Gnomad AFR exome

AF:

0.210

Gnomad AMR exome

AF:

0.0536

Gnomad ASJ exome

AF:

0.125

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0192

Gnomad FIN exome

AF:

0.0257

Gnomad NFE exome

AF:

0.0655

Gnomad OTH exome

AF:

0.0820

GnomAD4 exome

AF:

0.0623

AC:

90713

AN:

1455152

Hom.:

3679

Cov.:

AF XY:

0.0610

AC XY:

44119

AN XY:

723592

show subpopulations

Gnomad4 AFR exome

AF:

0.212

Gnomad4 AMR exome

AF:

0.0572

Gnomad4 ASJ exome

AF:

0.123

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.0197

Gnomad4 FIN exome

AF:

0.0281

Gnomad4 NFE exome

AF:

0.0625

Gnomad4 OTH exome

AF:

0.0774

GnomAD4 genome

AF:

0.100

AC:

15222

AN:

151952

Hom.:

1183

Cov.:

AF XY:

0.0954

AC XY:

7088

AN XY:

74276

show subpopulations

Gnomad4 AFR

AF:

0.211

Gnomad4 AMR

AF:

0.0776

Gnomad4 ASJ

AF:

0.119

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.0146

Gnomad4 FIN

AF:

0.0170

Gnomad4 NFE

AF:

0.0632

Gnomad4 OTH

AF:

0.107

Alfa

AF:

0.0262

Hom.:

142

Bravo

AF:

0.113

Asia WGS

AF:

0.0240

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency in ESP (all): 1450/12518=11.5% -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over