3-179242978-CT-C

Variant names:

• chr3-179242978-CT-C
• rs143962239
• NM_171830.2:c.753delA

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.485
• Publications: 7 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_171830.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNMB3	NM_171830.2	MANE Select	c.753delA	p.Val252TyrfsTer4	frameshift	Exon 3 of 3	NP_741981.1
	KCNMB3	NM_014407.3		c.765delA	p.Val256TyrfsTer4	frameshift	Exon 4 of 4	NP_055222.3
	KCNMB3	NM_171828.3		c.759delA	p.Val254TyrfsTer4	frameshift	Exon 4 of 4	NP_741979.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNMB3	ENST00000392685.7	TSL:1 MANE Select	c.753delA	p.Val252TyrfsTer4	frameshift	Exon 3 of 3	ENSP00000376451.2
	KCNMB3	ENST00000314235.9	TSL:1	c.765delA	p.Val256TyrfsTer4	frameshift	Exon 4 of 4	ENSP00000319370.5
	KCNMB3	ENST00000485523.5	TSL:1	c.699delA	p.Val234TyrfsTer4	frameshift	Exon 4 of 4	ENSP00000418536.1

Frequencies

GnomAD3 genomes AF: 0.100 AC: 15213 AN: 151834 Hom.: 1179 Cov.: 28

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

GnomAD2 exomes AF: 0.0624 AC: 15188 AN: 243254 AF XY: 0.0595

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 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.: 31 AF XY: 0.0610 AC XY: 44119 AN XY: 723592

African (AFR) AF: 0.212 AC: 7058 AN: 33262

American (AMR) AF: 0.0572 AC: 2492 AN: 43550

Ashkenazi Jewish (ASJ) AF: 0.123 AC: 3160 AN: 25616

East Asian (EAS) AF: 0.0000756 AC: 3 AN: 39688

South Asian (SAS) AF: 0.0197 AC: 1669 AN: 84596

European-Finnish (FIN) AF: 0.0281 AC: 1493 AN: 53140

Middle Eastern (MID) AF: 0.139 AC: 796 AN: 5712

European-Non Finnish (NFE) AF: 0.0625 AC: 69391 AN: 1109460

Other (OTH) AF: 0.0774 AC: 4651 AN: 60128

GnomAD4 genome AF: 0.100 AC: 15222 AN: 151952 Hom.: 1183 Cov.: 28 AF XY: 0.0954 AC XY: 7088 AN XY: 74276

African (AFR) AF: 0.211 AC: 8728 AN: 41352

American (AMR) AF: 0.0776 AC: 1184 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.119 AC: 412 AN: 3468

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5180

South Asian (SAS) AF: 0.0146 AC: 70 AN: 4804

European-Finnish (FIN) AF: 0.0170 AC: 180 AN: 10594

Middle Eastern (MID) AF: 0.171 AC: 50 AN: 292

European-Non Finnish (NFE) AF: 0.0632 AC: 4296 AN: 67988

Other (OTH) AF: 0.107 AC: 226 AN: 2112

Alfa AF: 0.0262 Hom.: 142

Bravo AF: 0.113

Asia WGS AF: 0.0240 AC: 86 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

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 v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.48
Mutation Taster		=197/3	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: rs143962239; hg19: chr3-178960766; COSMIC: COSV55894181; COSMIC: COSV55894181;